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transcript
2 Survey of parabens
Title:
Survey of parabens
Editing:
Dorthe Nørgaard Andersen and Poul Bo Larsen
DHI
Published by:
The Danish Environmental Protection Agency
Strandgade 29
1401 Copenhagen K, Denmark
www.mst.dk/english
Year:
2013
ISBN no.
978-87-93026-02-5
Disclaimer:
When the occasion arises, the Danish Environmental Protection Agency will publish reports and papers concerning
research and development projects within the environmental sector, financed by study grants provided by the Danish
Environmental Protection Agency. It should be noted that such publications do not necessarily reflect the position or
opinion of the Danish Environmental Protection Agency.
However, publication does indicate that, in the opinion of the Danish Environmental Protection Agency, the content
represents an important contribution to the debate surrounding Danish environmental policy.
Sources must be acknowledged.
Survey of parabens 3
Table of Content
Preface ...................................................................................................................... 5 Summary and Conclusion .......................................................................................... 7 Sammenfatning og konklusion .................................................................................. 9 1. Introduction ..................................................................................................... 12
1.1 Survey background ............................................................................................................... 12 1.2 Methods ................................................................................................................................. 12
1.2.1 Databases ............................................................................................................... 12 1.2.2 Companies, authorities and other organisations contacted ................................. 12
2. Identity of the substances ................................................................................. 13 2.1 Name and other identifiers of the substances ..................................................................... 13 2.2 Physico-chemical properties ................................................................................................ 14
3. Regulatory framework...................................................................................... 16 3.1 Classification ......................................................................................................................... 16
3.1.1 Harmonised classification in the EU ..................................................................... 16 3.1.2 Self-classifications in the EU ................................................................................. 16
3.2 The European chemical legislation; REACH ....................................................................... 18 3.3 Other regulations .................................................................................................................. 18
3.3.1 Cosmetics................................................................................................................ 18 3.3.2 Food ........................................................................................................................ 18 3.3.3 Pharmaceutical use ................................................................................................ 19
3.4 Waste water and solid waste regulations ............................................................................. 19 3.5 Regulatory and risk management initiatives ...................................................................... 20
3.5.1 Danish Advisory List for Self-Classification ........................................................ 20 3.6 Conclusion ............................................................................................................................. 21
4. Manufacture, import, export and use................................................................ 22 4.1 Manufacturing ..................................................................................................................... 22
4.1.1 Manufacturing sites .............................................................................................. 22 4.1.2 Manufacturing volumes ........................................................................................ 22
4.2 Import and export volumes ................................................................................................. 23 4.3 Information on use .............................................................................................................. 23
4.3.1 Use volumes .......................................................................................................... 23 4.3.2 Use in cosmetics .................................................................................................... 29 4.3.3 Use in food ............................................................................................................. 30 4.3.4 Use in pharmaceuticals ......................................................................................... 30 4.3.5 Use in other products ............................................................................................ 30 4.3.6 Estimated trends in use ........................................................................................ 32
4.4 Conclusions .......................................................................................................................... 33 5. Information on exposure .................................................................................. 34
5.1 Occupational exposure ........................................................................................................ 34 5.2 Consumer exposure ............................................................................................................. 34
5.2.1 Cosmetics............................................................................................................... 34 5.2.2 Food ....................................................................................................................... 35
4 Survey of parabens
5.2.3 Pharmaceuticals .................................................................................................... 36 5.3 Human exposure via the environment ............................................................................... 36 5.4 Conclusions ...........................................................................................................................37
6. Environmental hazard and fate assessment ...................................................... 38 6.1 Monitoring ........................................................................................................................... 38 6.2 Fate assessment ................................................................................................................... 38
6.2.1 Air .......................................................................................................................... 38 6.2.2 Soil ......................................................................................................................... 38 6.2.3 Water ..................................................................................................................... 38
6.3 Environmental hazard ......................................................................................................... 39 6.4 Conclusion ............................................................................................................................ 40
7. Human health hazard assessment .................................................................... 41 7.1 Absorption, metabolism, and excretion .............................................................................. 42
7.1.1 Absorption ............................................................................................................. 42 7.1.2 Metabolism and Excretion .................................................................................... 43
7.2 Estrogenic potential ............................................................................................................. 43 7.2.1 Methyl- and ethylparaben .................................................................................... 43 7.2.2 Propylparaben ....................................................................................................... 44 7.2.3 Butylparaben ......................................................................................................... 44 7.2.4 Isopropyl- and isobutylparaben ........................................................................... 44 7.2.5 Risk assessment considering the endocrine disrupting effects ........................... 44 7.2.6 Combination effects .............................................................................................. 44
7.3 Conclusions .......................................................................................................................... 45 8. Information on alternatives .............................................................................. 46
8.1 Conclusion ............................................................................................................................ 46 References .............................................................................................................. 47 Abbreviations .......................................................................................................... 54
Survey of parabens 5
Preface
The Danish Environmental Protection Agency’s List of Undesirable Substances (LOUS) is intended
as a guide for enterprises. It indicates substances of specific concern due to the actual consumption
in Denmark and for which the use should be reduced or eliminated completely. The first list was
published in 1998 and updated versions have been published in 2000, 2004 and 2009. The latest
version, LOUS 2009 (Danish EPA, 2011) includes 40 chemical substances and groups of substances
which have either been classified as dangerous or identified as problematic due to other concerns.
The criteria employed by the Danish EPA for inclusion of substances on the list include:
• Properties of concern according to the EU ‘List of hazardous substances’;
• Properties of concern identified using computer-based model calculations outlined in the
Danish EPA’s ‘Advisory list for self-classification of dangerous substances’ (the Self-
classification list);
• PBT/vPvB substances as identified by the EU;
• Substances on the EU ‘Priority list of substances for further evaluation of their role in
endocrine disruption’
Furthermore a tonnage threshold has been used. Substances used in quantities exceeding 100 tons
per year in Denmark and fulfilling any of the abovementioned criteria have been included in LOUS
2009. For substances which are the subject of special focus in Denmark, the tonnage threshold can
however be different.
Over the period 2012-2015 all 40 substances and substance groups on LOUS will be surveyed. The
surveys include collection of available information on the use and occurrence of the substances,
internationally and in Denmark, information on environmental and health effects, on alternatives
to the substances, on existing regulation, on monitoring and exposure and information regarding
ongoing activities under REACH among others.
The Danish EPA will on the basis of the surveys assess the need for any further regulation,
substitution/phase out, classification and labelling, improved waste management, development of
new knowledge or increased dissemination of information.
This survey concerns 6 substances of the paraben group: methyl-, ethyl-, propyl-, butyl-, isopropyl-
and isobutylparaben. It was thus decided to extend this survey to include four additional substances
compared to the ones listed on LOUS.
The reasons for including certain parabens (propyl- and butyl-) on LOUS were that the substances
have special focus in Denmark because of their listing on EU’s list of priorities substances due to
their endocrine disrupting effects. Also, one of the substances, butylparaben, was included on LOUS
because it was identified on the previous Danish Advisory List for Self-Classification as N; R50/53
(acute and chronic aquatic toxic), while propylparaben was identified as N; R50 (acute aquatic
toxicity).
6 Survey of parabens
The project ”Survey of Parabens” was carried out from June till December 2012.
The project was carried out by DHI, Denmark.
The project participants were:
• M.Sc. Dorthe Nørgaard Andersen, Project manager
• M. Sc. Pharm. Poul Bo Larsen, Quality supervisor
The preparation of this report has been supervised by a reference group consisting of:
• Lea Stine Tobiassen, Danish Environmental Protection Agency
• Louise Grave-Larsen, Danish Environmental Protection Agency
• Bettina Ørsnes Andersen, Danish Environmental Protection Agency
• Lærke Ambo Nielsen, Danish Environmental Protection Agency
• Mette Tingleff Skaanild, Danish Environmental Protection Agency
• Ulla Hansen Telcs, Danish industry
• Cathrine Berliner Boteju, The Association of Danish Cosmetics, Toiletries, Soap and Detergent
Industries
• Stine Fabricius, The Association of Danish Cosmetics, Toiletries, Soap and Detergent
Industries
• Annette Grossmann, Danish Veterinary and Food Administration
• Tina Zinck, Danish Health and Medicines Authority
The project was financed by the Danish Environmental Protection Agency.
The report reflects the author’s views and opinions, but not necessarily the views of the Danish
Environmental Protection Agency.
Survey of parabens 7
Summary and Conclusion
Parabens are esters of 4-hydroxybenzoic acid. They are used as preservatives in a wide range of
products including those for children, such as cosmetics, pharmaceuticals, consumer products like
pet care products, and in foods. They are used as single compounds and in combination to exert an
antimicrobial effect. They were first used in pharmaceuticals in the 1920’s, and since then have
found wide application because of their antimicrobial efficacy.
Propyl- and butylparabens were included in LOUS due to their potential endocrine disrupting
properties and their possible environmental effects.
Scarce information was received by the industry and authorities on total and application related use
volumes in and outside EU. Based on existing and available data retrieved from the internet, in view
of the general description of the substances, and especially in view of the numerous companies that
have pre-registered the substances under REACH, the use in various products and the overall
amount of parabens appears to be substantial. World-wide the main use areas are cosmetic
products, pharmaceuticals and food. Based on the data found in this survey, methyl- and
propylparaben are the most widely used parabens with methylparaben showing the highest use
volume. Data on use from the Nordic countries product registers indicate that the use of parabens
has declined from 2006-2007, when the level peaked, until 2010. However, the use volume in 2010
was at the same level as in 1999.
In the European Union (EU), the use of parabens is regulated by various types of regulation
depending on the use. Methylparaben is registered according to the European chemicals legislation
REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances), while
ethyl-, propyl-, butyl-, isopropyl- and isobutylparaben currently are only pre-registered under
REACH.
In cosmetic products 4-hydroxybenzoic acid, its salt and esters (the parabens) are currently
authorised as preservatives in cosmetic products under the Cosmetic Directive (76/768/EEC). The
maximum concentration of use is 0.4% (as acid) for one ester and 0.8% (as acid) for a mixture of
esters. These regulations are currently being discussed on the EU level due to an Opinion from the
Scientific Committee on Consumer Safety (SCCS) from 2010. Based on the potential estrogenic
effects of the parabens, this Opinion recommends lowering the limits for propyl- and butylparaben
to a maximum total concentration of 0.19% (as esters) or 0.14 (as acid) (SCCS, 2010). The Opinion
suggests maintaining the current concentration limit for methyl- and ethylparaben, while data on
isopropyl- and isobutylparaben are too limited for evaluation. In 2011 the Danish government
banned the use of some parabens in cosmetics intended for children up to three years of age. The
banned compounds are propyl-, isopropyl-, butyl- and isobutylparabens.
In the EU, only methyl- and ethylparaben are allowed as food additive and only for specific
applications (i.e., some forms of confectionery, surface treatment of dry meat products, cereal- or
potato-based snacks and coated nuts). Previously propylparaben was also allowed, but because of
its potential estrogenic effects the European Food Safety Authority (EFSA) was in 2006 not able to
determine an ADI for propylparaben. Therefore, it is no longer allowed as a food additive in the EU.
In the USA methyl- and propylparaben are regarded as GRAS (Generally Recognised As Safe)
substances, and may thus be added directly to food at a level not exceeding 0.1%. In the USA
parabens are used in a wide range of products.
In both the EU and the USA, the use of parabens in pharmaceuticals is allowed if it can be
documented that they are of no harm to the consumer. However, as seen in the EU for the
cosmetics, also the European Medicines Agency may possibly decide on a more strict regulation in
the future as initiatives are on-going regarding the parabens.
8 Survey of parabens
For the environment, the assessment of fate and hazard for parabens indicated a low toxicity. This
was despite the QSAR prediction on which the Advisory list for self-classification is based,
identifying propyl- and butylparaben as acutely toxic to aquatic organisms. Only few data regarding
the environmental toxicity of parabens were found. For the parabens, estimated risk ratios were
calculated as MEC/PNEC (measured environmental concentrations/predicted no effect
concentrations). The highest MEC/PNEC was (0.010) for propylparaben followed by butylparaben
(max. of 0.0086) and methylparaben (max. of 0.0042). These estimated low risk ratios (<<1) thus
indicate a low risk for environmental effects of parabens. Some studies have shown that parabens
may have estrogenic effects in fish. However, the effects are seen at concentrations much higher (µg
- mg) than actual environmental concentrations, as for instance in Spain and Japan (ng/L).
Human exposure to parabens occurs mainly through cosmetic products. An older USA estimation of
exposure indicates that only 20% will be through food, making cosmetics the main exposure route
for humans. Of the exposure through cosmetics, almost 100% will be dermal.
Concerns have been raised about the endocrine disrupting potential of parabens at high exposure
levels. Some studies in young male rats have shown adverse effects on sperm production and
testosterone levels following oral exposure to parabens, i.e. propyl- and butylparaben. However
other studies with the same study design and of a more recent date did not confirm these finding
even at very high doses. Both the studies with positive and negative findings on reproductive
toxicity have shortcomings, which makes it difficult to assess and weigh the results. Parabens are
known to be estrogenic in vitro and in uterotrophic assays in vivo, and estrogenicity appears to
increase with side chain length. Therefore, methyl-, ethyl-, propyl- and butylparaben are on the EU
list of potential endocrine disruptors in category 1. Isopropyl- and isobutylparaben are not on this
EU list. Category 1 substances are substances for which endocrine disrupting activity has been
documented in at least one study of a living organism and are given the highest priority for further
studies.
This project reveals that the method for evaluating parabens for their endocrine disruption
potential and their kinetics are still not agreed upon. In addition, discussions on the most relevant
NOEL/NOAEL and the dermal absorption values have not yet come to a conclusion. Thus,
considering the endocrine disrupting effects, a final risk assessment still awaits which
NOEL/NOAEL to use and which dermal absorption fraction to use, and to further identify the
overall exposure for children. Currently a new study concerning reproductive toxicity is being
assessed by the SCCS. Only few studies are available on the combined exposure to several parabens
from several products.
Alternatives to parabens could be preservatives that are approved for use in other areas. However,
before changing preservatives on a large scale, the sensitising potential of many other preservatives
must be borne in mind. Parabens themselves are rarely seen as sensitizers, although some of the
parabens have been self-classified as skin- or respiratory sensitizers. Technologies totally reducing
the need for preservation have not yet been marketed.
In conclusion, this survey has revealed that the most widely used parabens in EU are methyl- and
propylparaben. The major use is in cosmetics. In the EU parabens are controlled in the REACH,
cosmetics, pharmaceuticals and foods regulations. Stricter EU legislation is currently being
considered for parabens in cosmetics and pharmaceuticals due to the substances' potential for
endocrine disruption. In Denmark, a national band of 4 parabens was introduced in cosmetic
products intended for children up to three years old in 2011. Propyl- and butylparaben and their
isoforms are potential endocrine disrupters, and methyl-and ethylparaben potential weak endocrine
disrupters. For the environment, the assessment of fate and hazard for parabens indicates a low
toxicity. Alternatives could be other approved preservatives with a low toxicity profile or new
technology totally reducing the need for chemical preservation. However, no concrete solutions are
yet available.
Survey of parabens 9
Sammenfatning og konklusion
Parabener er estere af 4-hydroxybenzoesyre. De bruges som konserveringsmidler i en lang række
produkter som kosmetik, lægemidler, forbrugerprodukter som plejeprodukter til kæledyr samt i
fødevarer. De anvendes som enkeltstoffer og i kombination på grund af deres antimikrobielle effekt.
De blev første gang brugt i lægemidler i 1920’erne, og siden da har de fundet bred anvendelse på
grund af deres antimikrobielle effekt. Propyl-og butylparaben indgik i LOUS på grund af deres
potentielle hormonforstyrrende egenskaber og mulige miljøeffekter.
Der blev indhentet oplysninger fra industri og myndigheder på anvendelsesrelaterede
brugsmængder i og uden for EU, men kun modtaget få besvarelser. Baseret på eksisterende og
tilgængelige data hentet fra internettet og i betragtning af den generelle beskrivelse af stofferne -
navnlig i betragtning af de mange virksomheder, der har præregistreret stofferne under REACH,
vurderes den samlede anvendelse af parabener i forskellige produkter at være væsentlig. På
verdensplan er de vigtigste anvendelsesområder kosmetiske produkter, lægemidler og fødevarer. På
baggrund af de data, der er fundet i denne undersøgelse, er methyl-og propylparaben de mest
anvendte parabener med methylparaben som det stof, der anvendes i den største mængde. Data fra
de nordiske landes produktregistre tyder på, at brugen af parabener er faldet fra 2006-2007, hvor
niveauet toppede, til 2010. Dog var den anvendte mængde i 2010 på samme niveau som i 1999.
I Den Europæiske Union (EU) er brugen af parabener reguleret ved forskellige typer forordninger
afhængigt af brugen. Methylparaben er registreret i henhold til den europæiske kemikalielovgivning
REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances), mens
ethyl-, propyl-, butyl-, isopropyl- og isobutylparaben i øjeblikket kun er præ-registreret under
REACH.
4-Hydroxybenzoesyre, dens salte og estere (parabenerne) er tilladt som konserveringsmidler i
kosmetiske produkter under kosmetikdirektivet (76/768/EØF). Den maksimalt tilladte
koncentration er 0,4 % (som syre) for én ester og 0,8 % (som syre) for en blanding af estere. Disse
regler bliver i øjeblikket drøftet på EU-plan på grund af en rapport fra 2010 udarbejdet af Den
Videnskabelige Komité for Forbrugersikkerhed (VKF). Baseret på de potentielle østrogene effekter
af parabener anbefaler VKF at sænke grænserne for propyl- og butylparaben til en maksimal tilladt
koncentration på 0,19 % (som ester) eller 0,14 % (som syre) (VKF, 2010). VKF foreslår bibeholdelse
af den nuværende tilladte koncentration for methyl- og ethylparaben, mens data for isopropyl- og
isobutylparaben er for begrænset til en egentlig evaluering.
I 2011 forbød den danske regering anvendelsen af visse parabener i kosmetiske produkter beregnet
til børn op til tre år. De forbudte forbindelser er propyl-, isopropyl-, butyl- og isobutylparaben.
I EU er kun methyl- og ethylparaben tilladt som tilsætningsstof til fødevarer og kun til særlige
anvendelser (nogle typer konfekture, overfladebehandling af tørrede kødprodukter, korn- eller
kartoffel-baserede snacks samt overfladebehandlede nødder). Tidligere var propylparaben også
tilladt, men på grund af dets potentielle østrogene effekter var den Europæiske
Fødevaresikkerhedsmyndighed (EFSA) i 2006 ikke i stand til at bestemme en værdi for Acceptabelt
Dagligt Indtag (ADI) for propylparaben. Derfor er stoffet ikke længere tilladt som tilsætningsstof i
fødevarer i EU. I USA betragtes methyl- og propylparaben som GRAS (generelt anerkendte som
sikre) stoffer og kan således tilsættes direkte til fødevarer i en koncentration, der ikke overstiger 0,1
%. I USA anvendes parabener i en lang række fødevareprodukter.
Både i EU og USA er brugen af parabener i lægemidler tilladt, hvis det kan dokumenteres, at de ikke
udgør en risiko for forbrugeren. Men som det også ses i EU på kosmetikområdet, er Det Europæiske
Lægemiddelagentur i drøftelser om en eventuelt strengere regulering i fremtiden, da der er
initiativer i gang med hensyn til parabener.
10 Survey of parabens
Med hensyn til miljøet viser vurderingen af parabeners skæbne og fare en lav toksicitet. Dette til
trods for at QSAR forudsigelser, som Miljøstyrelsens vejledende liste til selvklassificering er baseret
på, angiver propyl- og butylparaben som akut toksiske for vandlevende dyr. Der blev kun fundet få
data vedrørende parabeners økotoksicitet. For parabenerne blev en risikokoefficient beregnet som
MEC/PNEC (målte miljø koncentrationer/forventede ingen-effekt-koncentrationer). Den højeste
MEC/PNEC var (0,010) for propylparaben efterfulgt af butylparaben (maks. 0,0086) og
methylparaben (maks. 0,0042). De beregnede lave risikokoefficienter (<< 1) indikerer således en
lav risiko for miljømæssige effekter af parabener. Nogle undersøgelser har vist, at parabener kan
have østrogene effekter på fisk. Dog ses virkningerne ved langt højere koncentrationer (ug - mg)
end de faktisk målte miljø-koncentrationer, som for eksempel i Spanien og Japan (ng/L).
Human eksponering for parabener sker hovedsageligt gennem kosmetiske produkter. En ældre
amerikansk eksponeringsvurdering viser, at kun 20 % af den samlede eksponering for parabener vil
være gennem fødevarer, hvilket vil sige, at eksponering via kosmetik er hovedeksponeringsvejen for
mennesker. Eksponeringen via kosmetik vil næsten udelukkende ske gennem huden.
Der er blevet udtrykt bekymring om parabeners potentielle hormonforstyrrende egenskaber ved
høje eksponerings-niveauer. Nogle undersøgelser i unge hanrotter har vist skadelige virkninger på
sædproduktionen og nedsatte testosteron-niveauer efter oral eksponering for parabener, dvs.
propyl- og butylparaben. Men andre studier med samme undersøgelsesdesign og af nyere dato
kunne ikke bekræfte disse fund selv ved meget høje doser. Både studierne med positive og negative
resultater for reproduktionstoksicitet har mangler, hvilket gør det vanskeligt at vurdere
resultaterne. Parabener vides at være østrogene in vitro og i uterotrofiske assays in vivo, og
østrogeniciteten øges tilsyneladende med sidekædelængden. Derfor er methyl-, ethyl-, propyl- og
butylparaben på EUs liste over potentielt hormonforstyrrende stoffer i kategori 1. Isopropyl- og
isobutylparaben er ikke på denne EU-liste. Kategori 1 stoffer er stoffer, hvor den
hormonforstyrrende effekt er dokumenteret i mindst én undersøgelse i en levende organisme.
Kategori 1 stoffer har den højeste prioritet for yderligere undersøgelser.
Dette projekt viser, at metoden til vurdering af parabeners potentielle hormonforstyrrende effekter
og kinetik stadig ikke er afklaret. Desuden er det endnu ikke konkluderet, hvilke NOEL/NOAEL
samt dermale absorptionsværdier, der er de mest relevante til en endelig risikovurdering. Der
mangler derfor endnu en afklaring af, hvilken NOEL/NOAEL og dermal absorptionsfraktion, der
skal bruges ved en endelig risikovurdering baseret på stoffernes hormonforstyrrende potentiale
samt yderligere at identificere den overordnede eksponering for børn. I øjeblikket bliver en ny
undersøgelse om reproduktionstoksicitet vurderet af VKF. Der er kun få undersøgelser tilgængelige
på kombineret eksponering for flere parabener fra flere produkter.
Alternativer til parabener kan være konserveringsmidler, der er godkendt til brug på andre
områder. Ved ændring af konserveringsmidler i stor skala skal det sensibiliserende potentiale af
mange andre konserveringsmidler dog tages i betragtning. Parabener i sig selv ses sjældent at være
sensibiliserende, selvom nogle af parabenerne er selvklassificeret som hud- eller
luftvejssensibiliserende. Teknologier, der helt fjerner behovet for kemisk konservering, er endnu
ikke blevet markedsført.
Sammenfattende har denne kortlægning vist, at de mest anvendte parabener i EU er methyl- og
propylparaben. Den primære anvendelse er i kosmetik. I EU reguleres parabener i REACH,
kosmetik-, lægemiddel- og fødevarelovgivningen. Strengere EU-lovgivning er i øjeblikket under
overvejelse for parabener anvendt i kosmetik og lægemidler på grund af stoffernes potentielle
hormonforstyrrende effekt. I 2011 blev der i Danmark indført et nationalt forbud mod 4 parabener i
kosmetiske produkter beregnet til børn op til tre år.
Propyl- og butylparaben og deres isoformer er potentielt hormonforstyrrende, og methyl- og
ethylparaben er potentielt svagt hormonforstyrrende stoffer. Med hensyn til miljøet viser
Survey of parabens 11
vurderingen af skæbne og fare, at parabener har en lav toksicitet. Alternativer til parabenerne kan
være andre godkendte konserveringsmidler med en lav toksicitetsprofil eller ny teknologi, der
reducerer behovet for kemisk konservering. Der er imidlertid ikke fundet nogen konkrete løsninger
endnu.
12 Survey of parabens
1. Introduction
1.1 Survey background Propyl- and butylparaben are included in LOUS due to their potential endocrine disrupting
properties and their possible environmental effects. In this report, surveys of the use, legislation,
exposure and environment and health properties of 6 parabens: methyl-, ethyl-, propyl-, butyl-,
isopropyl- and isobutylparaben are made. The additional parabens compared to the ones included
in LOUS were added to this survey as the parabens are often used in combination or alternatives to
one another (see table 1). The survey is based on existing information only.
Parabens are a group of substances used as preservatives. Chemically they resemble benzoic acid,
the preserving substance naturally present in lingon berries. They are highly effective in preventing
the growth of fungi and bacteria and are used to preserve products and greatly extend their shelf
life. Parabens have been used for decades as preservatives in the food, drug, personal care and
cosmetic products.
1.2 Methods 1.2.1 Databases
For this survey the data from the Nordic SPIN database has been used. Information from web
searches on the use and production of parabens was also reported.
1.2.2 Companies, authorities and other organisations contacted
Questionnaires were prepared for the industry, authorities and other organisations. For the
industry part industrial companies were selected among those who have reported notifications to
ECHA on all, several or one of the substances. They covered many different sectors, countries and
were mainly larger industries but also some smaller. About 50 different European industrial
companies have received a questionnaire. Additional 6 Chinese and Indian manufactures of
parabens were contacted for information about manufacture volumes. Only two answers from one
European company and one Indian manufacturer did return.
Among authorities, countries hosting companies selected above were prioritized. 11 countries
received the questionnaire (Australian, Canada, Finland, France, Germany, Italy, Netherlands,
Norway, Poland, Sweden and United Kingdom). Only one of them provided useful data. Two replied
that they did not have additional data than what is available from REACH. Two replied that
parabens are not substances of highest priority and therefore they have no data. One authority
informed that they have not the resources to find available data based on the short deadline. Along
with that some Danish industrial organizations, Danish EPA, the Danish Veterinary and Food
Administration, the Danish Health and Medicines Authority and other contact persons have
provided data to this present survey on parabens.
Survey of parabens 13
2. Identity of the substances
2.1 Name and other identifiers of the substances Six different parabens are being evaluated in this report. The substances and their identity are
presented in table 1. TABLE 1 NAME AND OTHER IDENTIFIERS OF THREE OF THE SIX EVALUATED PARABEN SUBSTANCES (HSDB)
EC name: methyl 4-hydroxybenzoate ethyl 4-hydroxybenzoate propyl 4-hydroxybenzoate
EC number: 202-785-7 204-399-4 202-307-7
CAS number: 99-76-3 120-47-8 94-13-3
Synonyms: Methylparaben; Benzoic acid,
p-hydroxy-, methyl ester; p-
hydroxybenzoic methyl ester
Ethylparaben; Benzoic acid, p-
hydroxy-, ethyl ester; p-
hydroxybenzoic ethyl ester
Propylparaben; Benzoic acid,
p-hydroxy-, propyl ester; p-
hydroxybenzoic propyl ester
Molecular
formula: C8H8O3 C9H10O3 C10H12O3
Molecular
weight range: 152.15 166.17 180.20
Structure:
EC name: butyl 4-hydroxybenzoate isopropyl 4-
hydroxybenzoate
isobutyl 4-
hydroxybenzoate
EC number: 202-318-7 224-069-3 224-208-8
CAS number: 94-26-8 4191-73-5 4247-02-3
Synonyms: Butylparaben; Benzoic acid, p-
hydroxy-, butyl ester; p-
hydroxybenzoic butyl ester
Isopropylparaben; Benzoic
acid, p-hydroxy-, isopropyl
ester; p-hydroxybenzoic
isopropyl ester
Isobutylparaben; Benzoic acid,
p-hydroxy-, isobutyl ester; p-
hydroxybenzoic isobutyl ester;
Molecular
formula: C11H14O3 C10H12O3 C11H14O3
Molecular
weight range: 194.23 180.20 194.23
Structure
14 Survey of parabens
2.2 Physico-chemical properties TABLE 2 PHYSICAL-CHEMICAL PROPERTIES FOR METHYL-4-HYDROXYBENZOATE AND ETHYL-4-HYDROXYBENZOATE (HSDB)
Property Methyl-4-hydroxybenzoate
Ethyl-4-hydroxybenzoate
Ref. REACH, Annex, §
Physical state Colourless crystals or white crystalline powder
Small, colorless crystals or white powder
VII, 7.1
Melting/freezing point 131°C 116 °C VII, 7.2
Boiling point 270-280°C 297-298 °C VII, 7.3
Relative density No data found No data found VII, 7.4
Vapour pressure 2.37 x 10-4 mm Hg 9.29 x 10-5 mm Hg VII, 7.5
Surface tension No data found No data found VII, 7.6
Water solubility (mg/L) 2.50 x 103 mg/L 8.85 x 102 mg/L VII, 7.7
Partition coefficient n-octanol/water (log value)
1.96 2.47 VII, 7.8
Stability in organic solvents and identity of relevant degradation products
No data found No data found XI, 7.15
Dissociation constant pKa = 8.4 pKa = 8.34 XI, 7.16 TABLE 3 PHYSICAL-CHEMICAL PROPERTIES FOR PROPYL-4-HYDROXYBENZOATE AND BUTYL-4-HYDROXYBENZOATE (HSDB)
Property Propyl-4-hydroxybenzoate
Butyl-4-hydroxybenzoate
Ref, REACH Annex, §
Physical state White crystals Small, colorless crystals or powder
VII, 7.1
Melting/freezing point 96-97 °C 68-69 °C VII, 7.2
Boiling point No data found No data found VII, 7.3
Relative density 1.063 No data VII, 7.4
Vapour pressure 5.55 x 10-4 mm Hg 1.86 x 10-4 mm Hg VII, 7.5
Surface tension No data found No data found VII, 7.6
Water solubility (mg/L) 5.00 x 102 mg/L 2.07 x 102 mg/L VII, 7.7
Partition coefficient n-octanol/water (log value)
3.04 3.57 VII, 7.8
Stability in organic solvents and identity of relevant degradation products
No data found No data found XI, 7.15
Dissociation constant pKa = 7.91 pKa = 8.47 XI, 7.16
Survey of parabens 15
TABLE 4 PHYSICAL-CHEMICAL PROPERTIES FOR ISOPROPYL-4-HYDROXYBENZOATE AND ISOBUTYL-4-HYDROXYBENZOATE (CIR, 2008)
Property Isopropyl-4-hydroxybenzoate
Isobutyl-4-hydroxybenzoate
REACH ref Annex, §
Physical state No data found No data found VII, 7.1
Melting/freezing point No data found No data found VII, 7.2
Boiling point No data found No data found VII, 7.3
Relative density No data found No data found VII, 7.4
Vapour pressure No data found No data found VII, 7.5
Surface tension No data found No data found VII, 7.6
Water solubility (mg/L) No data found No data found VII, 7.7
Partition coefficient n-octanol/water (log value)
2.91 3.4 VII, 7.8
Stability in organic solvents and identity of relevant degradation products
No data found No data found XI, 7.15
Dissociation constant No data found No data found XI, 7.16
16 Survey of parabens
3. Regulatory framework
Information on the regulatory framework that covers the use of parabens has been sought national
in Denmark, in the EU and globally for the following areas:
• The European chemicals legislation REACH (Registration, Evaluation, Authorisation and
Restriction of Chemical substances)
- Harmonised classification
- Self-classification
• Cosmetic legislation
• Food legislation
• Pharmaceuticals legislation
• Waste regulation
In addition, other national and European initiatives regarding the regulation of parabens are
included in this chapter.
3.1 Classification 3.1.1 Harmonised classification in the EU
None of the six parabens are assigned a harmonised classification and labelling code according to
the classification and Labelling of Products (CLP) regulation: Regulation (EC) No 1272/2008
(Annex VI, part 3, Table 3.1).
3.1.2 Self-classifications in the EU
In the classification and labelling (C&L) inventory (database) notifiers have reported classifications
for parabens (ECHA, 2012). In table 5 the spectrum of different classifications, reported as of
November 17 2012, are shown.
TABEL 5 THE (CLP) SELF-CLASSIFICATION NOTIFIED BY MOST MANUFACTURERS AND IMPORTERS ACCORDING TO ECHA ‘CLASSIFICATION AND LABELLING (C&L) INVENTORY’
Substance
No. of
notifiers
(total)
Classification
No. of notifiers
reporting a
specific
classification Hazard Class
and Category
Code
Hazard
Statement
Code
Methyl-4-
hydroxybenzoate
1908
Skin Irrit.2
Eye Irrit.2
STOT SE3
H315
H319
H335
47%
Not classified
43%
Muta.2
Resp. Sens.1
Aquatic Chronic 3
H341
H334
H412
Fewer than 10%
Survey of parabens 17
Substance
No. of
notifiers
(total)
Classification
No. of notifiers
reporting a
specific
classification Hazard Class
and Category
Code
Hazard
Statement
Code
Ethyl-4-
hydroxybenzoate 767
Not classified 46%
Asp.tox.3
Skin Irrit.2
Skin Sens.1
Eye Irrit.2
H304
H315
H317
H319
38%
Acute Tox 4
Resp. Sens.1
STOT SE 3
H302
H334
H335
Fewer than 16%
Propyl-4-
hydroxybenzoate 1566
Skin Irrit.2
Eye Irrit.2
STOT SE 3
H315
H319
H335
55%
Not classified 29%
Skin Sens.1
Eye Dam.1
Aquatic Acute 1
H317
H318
H400
Fewer than 16%
Butyl-4-
hydroxybenzoate 633
Skin Irrit.2
Eye Irrit.2
STOT SE 3
H315
H319
H335
50%
Not classified 40%
Eye Dam.1
Aquatic Chronic4
H318
H413 Fewer than 10%
Isopropyl-4-
hydroxybenzoate 67
Eye Irrit.2 H319 43%
Acute tox. 4
Eye Dam. 1
H302
H318 34%
Not classified 16%
isobutyl-4-hydroxybenzoate 262
Not classified 85%
Eye Dam. 1
H318
11%
Aquatic Acute 1 H400 2%
H302; Harmful if swallowed
H304; May be fatal if swallowed and enters airways
H315; Causes skin irritation
H317; May cause an allergic skin reaction
H318; Causes serious eye damage
H319; Causes serious eye irritation
H334; May cause allergy or asthma symptoms or breathing
difficulties if inhaled
H335; May cause respiratory irritation
H341; Suspected of causing genetic defects
H400; Very toxic to aquatic life
H412; Harmful to aquatic life with long lasting effects
H413; May cause long lasting harmful effects to aquatic life
18 Survey of parabens
As can be seen in table 5 the substances are typically self-classified for local irritation in relation to
skin, eyes and the respiratory tract and for respiratory or skin sensitisation, whilst only a small
proportions of notifications include the end-point of aquatic toxicity.
3.2 The European chemical legislation; REACH The parabens are regulated within the EU. Methylparaben are registered according to the European
chemical legislation REACH, while ethyl-, propyl-, butyl-, isopropyl- and isobutylparaben are
currently only pre-registered by numerous notifiers. For methylparaben the registrant has reported
long-term DNEL values for both dermal and oral exposure of 1.04 mg/ kg bw/day and for
inhalation a long-term DNEL value of 3.62 mg/m3 in relation to the general population.
3.3 Other regulations Parabens are used in a broad spectrum of products not regulated under REACH. Other pieces of
legislation by which parabens are regulated are presented below.
3.3.1 Cosmetics
Some parabens are restricted both in and outside EU. As the only member state in the EU,
Denmark has introduced a ban at national level. For the use of parabens as preservative in
cosmetics the restrictions are the following:
In the EU:
4-Hydroxybenzoic acid, its salt and esters (parabens) are currently authorised in Annex VI, entry 12
of the Cosmetic Directive (76/768/EEC) at a maximum use concentration of 0.4% (as acid) for one
ester and 0.8% (as acid) for a mixture of esters.
National regulation in Denmark:
In 2011, the Danish government banned the use of some parabens (propyl-, isopropyl-, butyl- and
isobutylparabens) in cosmetic products intended for children up to three years old as a
precautionary measure, as children might be especially vulnerable to endocrine disrupting effects
(BEK no. 166 24/02/2011).
In the USA:
All six selected parabens are allowed in cosmetics without any concentration limit in the USA (FDA,
2012a). The Cosmetic Ingredient Review (CIR) reviewed the safety of methylparaben,
propylparaben, and butylparaben in 1984 and concluded they were safe for use in cosmetic
products at levels up to 25%. Typically parabens are used at levels ranging from 0.01 to 0.3%. In
2005 this evaluation was reviewed again. However, after considering the margins of safety for
exposure of women and infants, CIR determined that there was no need to change its original
conclusion that parabens are safe for use in cosmetics. The FDA is aware of the possible estrogenic
effects of some parabens, but believes that at the present time there is no reason for consumers to
be concerned about the use of cosmetics containing parabens. However, the FDA will continue to
evaluate new data in this area (FDA, 2007).
3.3.2 Food
In the EU:
Two of the selected parabens may be used as preservative in food:
• Ethylparaben, E 214, its sodium salt E 215
• Methylparaben, E 218, its sodium salt E 219.
The two parabens are allowed in confectionery (excluding chocolate) in amounts up to 300 mg
parabens/kg. Methyl- and ethylparaben are also allowed as surface treatment of dried meat
Survey of parabens 19
products, cereal- or potato-based snacks and coated nuts (maximum 300 mg/kg) (Regulation (EU)
No. 1129/2011).
On July 13th 2004 the European Food Safety Authority (EFSA) established a group ADI of 0 - 10
mg/kg body weight for the sum of methyl and ethyl p-hydroxybenzoic acid esters and their sodium
salts. EFSA considered that propylparaben should not be included in this group ADI because
propylparaben, contrary to methyl- and ethylparaben, had effects on sex hormones and the male
reproductive organs in juvenile rats. Therefore, due to lack of a clear no observed adverse effect
level (NOAEL), EFSA was unable to recommend an ADI for propylparaben. It was necessary to
withdraw E 216 propyl p-hydroxybenzoate and E 217 sodium propyl p-hydroxybenzoate from
Regulation (EU) No. 1129/2011.
In the USA:
Methyl- and propylparaben added directly to human food are affirmed as generally recognized as
safe (GRAS) (FDA, 2012b), and are GRAS for use at a level not exceeding 0.1% in accordance with
good manufacturing or feeding practice (FDA, 2012c).
This conclusion was based on the following information: Upon consumption of parabens in
amounts greatly exceeding those current in the normal diet in the USA population, there are no
short-term toxicological consequences in the rat, rabbit, cat, dog, or man and no long-term
toxicological consequences in rats. In addition, there is no evidence that consumption of the
parabens as food ingredient has had an adverse effect on man in the 40 years they have been so
used in the US. In the light of these observations, the Select Committee concluded: There is no
evidence in the available information on the two parabens methyl and propyl p-hydroxybenzoic acid
that demonstrates a hazard to the public when the substances are used at levels that are now
current or that might reasonably be expected in future (FDA, 2012d).
Other countries:
Several other countries, including Canada, Japan, and the Philippines have also approved the use of
parabens as antimicrobial food additives (Soni et al, 2002).
3.3.3 Pharmaceutical use
In the EU:
Parabens as preservatives are allowed in pharmaceuticals in the EU, but as for other preservatives,
the use and concentration must be justified accordingly to risk (EMEA, 2006). In addition, the
pharmaceutical legal and regulatory context and the evaluation process all imply that similar
principles of risk assessment are applied both to excipients and to active substances where
appropriate. However, excipients have only an indirect benefit for the patient, as part of a medicinal
product. Therefore, any risk identified for an excipient, and in particular a CMR substance, would
be acceptable only on certain conditions. These are either that this excipient cannot be substituted
by a safer alternative available or that the toxicological effects of the excipient in animal models are
considered not relevant for humans (e.g. species-specific or very large safety ratio), or that the
overall benefit of the product outweighs the risk posed by the excipient (EMA, 2009).
In the US:
Parabens are permitted in pharmaceutical products. Preservatives are considered inactive
ingredients and must meet the requirements specified in the Code of Federal Regulations Title 21,
§330.1 (FDA, 2012e). Accordingly, the preservatives must be a suitable ingredient that is safe and
does not interfere with effectiveness of the medicinal product.
3.4 Waste water and solid waste regulations No data were found on this topic.
20 Survey of parabens
3.5 Regulatory and risk management initiatives In the EU there are initiatives to strengthen the regulation of some parabens when they are used as
preservatives in cosmetics. In a review of the most up-to-date scientific information, the Scientific
Committee on Consumer Safety (SCCS) confirmed that for the smaller parabens (methyl-and
ethylparaben), the current concentration limit is considered safe (SCCS, 2010). For propyl- and
butylparaben, the SCCS recommends lowering the limit to a maximum total concentration of 0.19%
(as ester) or 0.14% (as acid) for each of the substances (SCCS, 2010). For other, less used, parabens
(isopropyl-, isobutylparabens), only a very limited amount of information is available, and the
potential risk could not be evaluated (SCCS, 2010).
Also for use in pharmaceutical products, initiatives are being considered to adjust the acceptable
levels of methyl- and propylparaben in oral medicinal products. At the moment a ”Reflection paper
on the presence of parabens in human medicinal products” is being prepared.
Methyl-, ethyl-, propyl- and butylparaben are on the EU list of potential endocrine disruptors which
are to be studied further for endocrine-disrupting properties (EU, 2012). They are entered as
category 1 substances, which are substances for which endocrine activity have been documented in
at least one study of a living organism. These substances are given the highest priority for further
studies. Furthermore, propyl- and butylparaben were both added to the SIN list (Substitute It Now)
at the latest update of the database (SIN list 2.0). The SIN project is an NGO-driven European
project to speed up the transition to a toxic-free world with the purpose to identify substances of
very high concern according to REACH criteria. Propyl- and butylparaben are considered to belong
to this category solely due to their potential endocrine disrupting properties.
3.5.1 Danish Advisory List for Self-Classification
Parabens are found in the Danish Advisory list for CLP self-classification of dangerous substances’,
which is based on QSAR predictions (Danish EPA, 2010). The self-classifications for the parabens
are shown in table 6.
TABLE 6 CLP SELF-CLASSIFICATION ACCORDING TO THE DANISH ‘ADVISORY LIST FOR CLP SELF-CLASSIFICATION OF DANGEROUS SUBSTANCES’
Substance CAS No. Classification
Health*/
Classification
Environment*
Methyl-4-hydroxybenzoate 99-76-3 Muta2 -
Ethyl-4-hydroxybenzoate 120-47-8 Muta2 Acute1
Propyl-4-hydroxybenzoate 94-13-3 - Acute1
Chronic1
Butyl-4-hydroxybenzoate 94-26-8 - Acute1
Isopropyl-4-hydroxybenzoate 4191-73-5 SkinSens1 -
isobutyl-4-hydroxybenzoate 4247-02-3 - Acute1
* - : not listed
Muta2: mutagenic category 2
Acute1: Aquatic acute toxicity category 1
Chronic1: Aquatic chronic toxicity category1
SkinSens1: Skin sensitizer category 1
Survey of parabens 21
3.6 Conclusion Due to the endocrine disrupting potential of some of the parabens, the substances are restricted
both in the EU, elsewhere in the world, and a national ban was implemented in Denmark in 2011.
In the European Union (EU), the use of parabens is regulated by various types of regulation
depending on the use. Methylparaben is registered according to the European chemicals legislation
REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances), while
ethyl-, propyl-, butyl-, isopropyl- and isobutylparaben currently are only pre-registered under
REACH.
In cosmetic products 4-hydroxybenzoic acid, its salt and esters (the parabens) are currently
authorised as preservatives in cosmetic products at a maximum concentration of use is 0.4% (as
acid) for one ester and 0.8% (as acid) for a mixture of esters. The limits are currently being
discussed on the EU level due to an Opinion from the Scientific Committee on Consumer Safety
(SCCS) from 2010. Based on the potential estrogenic effects of the parabens, this Opinion
recommends lowering the limits of propyl- and butylparaben to a maximum total concentration of
0.19% (as ester) or 0.14 (as acid) (SCCS, 2010). The Opinion suggests maintaining the current
concentration limit for methyl- and ethylparaben, while data on isopropyl- and isobutylparaben are
too limited for evaluation.
In 2011 the Danish government banned the use of some parabens in cosmetics intended for children
up to three years of age. The banned compounds are propyl-, isopropyl-, butyl- and
isobutylparabens.
In the EU, only methyl- and ethylparaben are allowed as food additive and only for specific
applications (i.e., confectionery, surface treatment of dry meat products, cereal- or potato-based
snacks and coated nuts). Previously propylparaben was also allowed, but because of its potential
estrogenic effects the European Food Safety Authority (EFSA) was in 2006 not able to determine an
ADI for propylparaben. Therefore, it is no longer allowed as a food additive in the EU. In the USA
methyl- and propylparaben are regarded as GRAS (Generally Recognised As Safe) substances, and
may thus be added directly to food at a level not exceeding 0.1%. In the USA parabens are used in a
wide range of products.
In both the EU and the USA, the use of parabens in pharmaceuticals is allowed if it can be
documented that they are of no harm to the consumer. However, as seen in the EU for the
cosmetics, also the European Medicines Agency may possibly decide on a more strict regulation in
the future as initiatives are on-going regarding the parabens.
22 Survey of parabens
4. Manufacture, import, export and use
The literature indicates that parabens are primarily used as preservatives in cosmetics, food and
pharmaceuticals. However, other products like cleaning agents, biocidal products and pet care
products may also contain parabens.
4.1 Manufacturing 4.1.1 Manufacturing sites
Several manufacturing sites are found in Europe, USA and Asia. Based on searches on the internet
it was established that a lot of manufactures are located in India and China. Several of them have
been contacted during this survey, but none of them wanted to participate in the survey.
4.1.2 Manufacturing volumes
Based on the large amount of companies pre-registration the substances in the EU it can be
deduced that the manufacture and import of the substances is substantial. It has not been possible
to collect/find a total amount of manufacturing volume for each of the parabens even though the
information has been looked for at many places and several companies has been asked for data.
Information on production and/or use of parabens in the USA was identified from the USA Non-
confidential Inventory Update Reporting production Volume information (Table 7). This is however
only documenting the production/use from 1986 to 2002 and is therefore regarded as data of lower
value.
TABLE 7 THE PRODUCTION OF PARABENS IN USA (THE PRODUCTION VALUES ARE SHOWN IN TONNES PER YEAR)
Year Methyl- Ethyl- Propyl- Butyl- Isopropyl Isobutyl
1986 250 – 500 5 – 250 5– 250 5 – 250 - -
1990 500 – 5000 5 – 250 250 – 500 5 - 250 - -
1994 500 – 5000 - 250 – 500 5 - 250 - -
1998 250 – 500 - 5 – 250 - - -
2002 5 - 250 5 - 250 5 – 250 - - -
“-“: No information given (USA Non-confidential Inventory Update Reporting production Volume information)
Even though based on old data, the data indicates that the parabens produced in largest amounts
have been methyl-, and propylparaben, but in 2002 the level of methyl-, ethyl- and propylparaben
is the same. No information was available on the iso-compounds. There appears to be decrease in
consumption in 2002. However, more recent data are lacking.
Survey of parabens 23
4.2 Import and export volumes Parabens are produced all over the world, and many companies import parabens from
manufacturers in Asia and US.
Non-confidential data collected during the survey was received from the Danish and Finnish EPAs
product registers and shown in table 8 and 9. This information shows that methylparaben is the
substance imported the most in Denmark and in Finland. In Denmark, the use volume of
propylparaben is the second highest.
TABLE 8 INFORMATION OF USE VOLUMES FROM THE DANISH PRODUCT REGISTERS (2011), DATA IS SHOWN AS TON PER YEAR
Substance Use Volume
Methylparaben 0.689
Ethylparaben 0.042
Propylparaben 0.393
Butylparaben 0.005
Iso-propylparaben -
Iso-butylparaben 0.004
TABLE 9 INFORMATION OF IMPORT VOLUMES FROM THE FINNISH PRODUCT REGISTER FROM 2011. DATA ARE SHOWN AS TON PER YEAR
Substance Manufacture
(tonnes)
Imports
Tonnes / Origin
Relevant
year(s)
Methylparaben 0 1.8 N/A 2011
Ethylparaben 0 0.2 N/A 2011
Propylparaben 0 0.2 N/A 2011
Butylparaben 0 N/A N/A 2011
Iso-propylparaben 0 0 N/A 2011
Iso-butylparaben 0 N/A N/A 2011
N/A: Not available
4.3 Information on use Parabens has been used for several decades mainly as preservative in cosmetics covered by the
Council Directive 76/768/EEC, but is also used as preservative in pharmaceuticals, food, pet care
products, biocides etc.
4.3.1 Use volumes
From the Nordic SPIN database (“Substances in Preparations in the Nordic Countries”) information
of use volumes has been retrieved. The SPIN database is the result of a common Nordic initiative to
gather non-confidential, summarized information from the Nordic product registers on the
common use of chemical substances in different types of products and industrial areas. All the data
are summarized and no references can be made to specific concentrations of any given substance in
any kind of product. The Nordic product registers are among the most comprehensive product
registers in the world with regard to completeness of information and the number of registered
products and substances. Of the Nordic product registers, the Danish and Swedish product registers
24 Survey of parabens
contain information on the largest numbers of products and the highest proportion of products on
the market. In Sweden, the declaration requirements are based on the customs tariff codes, so that
as a general rule, they apply to all chemical products (substances and preparations). The Swedish
register therefore contains more products than those that are classified as dangerous according to
EU legislation. In Norway, declaration is mandatory for all products to which the Regulations
relating to the classification, labelling, etc. of dangerous chemicals (the Chemical Labelling
Regulations) apply, including consumer products. These regulations implement EU directives on
the classification, labelling, etc. of chemicals in Norwegian legislation.
The requirements for declaration to the Finnish and Danish product registers are also based on
these directives (in Denmark, declaration is limited to dangerous products for professional use), but
there are additional extensive national rules for notification. In Finland these additional
requirements for example apply to chemicals that cause danger although they are not classified, and
in Denmark they apply to chemicals that cause danger although they are not classified and solvents,
pesticides and biocides.
All four countries exempt products that come under legislation on foodstuffs and medicinal
products from mandatory declaration. Additionally, it is important to note that the use categories in
the database do not include all potential uses of the parabens; e.g. the duty to declare products to
the product registers does not apply to cosmetic products, and therefore these use volumes do not
cover the total use volume of the parabens. However, the figures can give a rough estimate,
especially of the use trends.
In figure 1, 3, 5 and 7 the total amount of parabens in combination with the number of products
containing the substances are illustrated.
4.3.1.1 Methylparaben
The total use volume of methylparaben registered in Sweden, Denmark, Finland and Norway from
the period from 1999 to 2010 (data indirectly retrieved from the Nordic SPIN database) is shown in
Figure 1. The total use volume and the number of products containing methylparaben for each
separate country are shown in Figure 2. It is observed in figure 1 that the use volume of
methylparaben increased from 1999 until 2005-2006 (peaking at about 60 ton) and then has
decreased until 2010. The level in 2010 is at the same level as seen in 2002. At the same time the
number of preparations containing methylparaben (figure 2) has remained on almost the same level
indicating that the preparations contains a lower concentration of methylparaben in 2010 than in
2005-2006.
FIGURE 1 THE TOTAL AMOUNT OF METHYLPARABEN REGISTERED IN
SWEDEN, DENMARK, FINLAND AND NORWAY (DATA INDIRECTLY
RETRIEVED FROM THE NORDIC SPIN DATABASE)
Survey of parabens 25
FIGURE 2 THE TOTAL USE OF METHYLPARABEN AND THE NUMBER OF PRODUCTS. THE DATA COVERS A
PERIODE FROM 1999 TO 2010 FOR SWEDEN, DENMARK, FINLAND AND NORWAY SEPERATELY (DATA
RETRIEVED FROM THE SPIN DATABASE)
4.3.1.2 Ethylparaben
The total use volume of ethylparaben registered in Sweden, Denmark, Finland and Norway from the
period from 1999 to 2010 (data indirectly retrieved from the Nordic SPIN database) is shown in
Figure 3. The total use volume and the number of products containing ethylparaben for each
separate country are shown in Figure 4. It is observed in figure 3 that the use volume of
ethylparaben is varying from year to year from 1 tonnes in 2004 to a peak of 4.5 tonnes in 2007 and
in 2010 being at a low level compared to 2007. At the same time the number of products containing
ethylparaben (figure 4) has remained on almost the same level indicating that the products contains
a lower concentration of ethylparaben in 2010 than in 2007.
FIGURE 3 THE TOTAL AMOUNT OF ETHYLPARABEN REGISTERED IN SWEDEN,
DENMARK, FINLAND AND NORWAY (DATA INDIRECTLY RETRIEVED FROM THE
NORDIC SPIN DATABASE)
26 Survey of parabens
FIGURE 4 THE TOTAL USE OF ETHYLPARABEN AND THE NUMBER OF PRODUCTS. THE DATA COVERS A
PERIODE FROM 1999 TO 2010 FOR SWEDEN, DENMARK, FINLAND AND NORWAY SEPERATELY (DATA
RETRIEVED FROM THE SPIN DATABASE)
4.3.1.3 Propylparaben
The total use volume of propylparaben registered in Sweden, Denmark, Finland and Norway from
the period from 1999 to 2010 (data indirectly retrieved from the Nordic SPIN database) is shown in
Figure 5. The total use volume and the number of products containing propylparaben for each
separate country are shown in Figure 6. As for methylparaben, it is observed in figure 5 that the use
volume of propylparaben increased from 1999 until 2005-2006 (peaking at about 32 ton) and then
has decreased until 2010. The level in 2010 is at the same level as seen in 1999. At the same time the
number of products containing propylparaben (figure 6) has remained on almost the same level or
only a slight decrease. This could indicate a lower mean concentration of propylparaben in the
products 2010 compared to the concentration in 2005-2006.
Survey of parabens 27
FIGURE 5 THE TOTAL AMOUNT OF PROPYLPARABEN REGISTERED IN
SWEDEN, DENMARK, FINLAND AND NORWAY (DATA INDIRECTLY RETRIEVED
FROM THE NORDIC SPIN DATABASE)
FIGURE 6 THE TOTAL USE OF PROPYLPARABEN AND THE NUMBER OF PRODUCTS. THE DATA COVERS A
PERIODE FROM 1999 TO 2010 FOR SWEDEN, DENMARK, FINLAND AND NORWAY SEPERATELY (DATA
RETRIEVED FROM THE SPIN DATABASE)
4.3.1.4 Butylparaben
The total use volume of butylparaben registered in Sweden, Denmark, Finland and Norway from
the period from 1999 to 2010 (data indirectly retrieved from the Nordic SPIN database) is shown in
Figure 7. The total use volume and the number of products containing butylparaben for each
separate country are shown in Figure 8. The use volume data for butylparaben has a slight peculiar
course (figure 7). The use volume is almost constant from 1999 to 2008 (about 1.1 ton), whereas the
28 Survey of parabens
volume decrease until “0” in 2009. However, at the same time the number of products containing
butylparaben (figure 8) does not decline to 0 at 2009! In Sweden and Denmark there are still
several products in 2009 and 2010 although the volume is registered as “0” in this period. This
could be due to error in the data retrieved from the SPIN database.
FIGURE 7 THE TOTAL AMOUNT OF BUTYLPARABEN REGISTERED IN SWEDEN,
DENMARK, FINLAND AND NORWAY (DATA INDIRECTLY RETRIEVED FROM THE
NORDIC SPIN DATABASE)
FIGURE 8 THE TOTAL USE OF BUTYLPARABEN AND THE NUMBER OF PRODUCTS. THE DATA COVERS A
PERIODE FROM 1999 TO 2010 FOR SWEDEN, DENMARK, FINLAND AND NORWAY SEPERATELY (DATA
RETRIEVED FROM THE SPIN DATABASE)
Survey of parabens 29
4.3.1.5 Isopropylparaben and isobutylparaben
No data is available in the Nordic SPIN database. No data on use volumes found other places, but
several papers and links on the internet suggests that the use volume of isopropyl- and isobutyl
paraben are limited within EU (SCCS, 2011).
4.3.2 Use in cosmetics
Parabens are widely used as preservatives in cosmetics worldwide. The substances are present in a
large variety of products including products for children. The products include face, body and hand
creams, lotions and moisturizers; eye makeup products; foundation and other makeup products;
night creams and lotions; cleansing products; hair conditioners; bubble baths; shampoos; mud
packs; underarm deodorants and skin lighteners (Soni et al, 2002). Methyl paraben and propyl
paraben are the most commonly used preservatives in cosmetics. Rather old data from 1984
indicates that parabens are found in all types of cosmetic formulations and have a use in over
13,200 formulations (Soni et al, 2002). Parabens have excellent chemical stability in relation to pH
(effective between pH 4.5 and 7.5) and temperature and formulate well because they have no
perceptible odour or taste, are practically neutral, do not produce discoloration, and do not cause
hardening or ‘‘muddying’’ (Soni et al, 2002).
The Danish Association of Danish Cosmetics, Toiletries, Soap and Detergent Industries did a survey
in 2010 asking their members regarding the use of parabens in children products. The survey
showed that, whit a few temporary exceptions, propyl- and butylparaben were no longer used in
cosmetic products for children under three years of age (SPT, 2010).
FIGURE 9 THE USE OF METHYLPARABEN AND PROPYLPARABEN IN COSMETICS BASED ON AMOUNT (TONNES) AND
NUMBER OF PRODUCTS. THE DATA IS RETRIVED FROM THE NORDIC SPIN DATABASE. THERE IS NO DUTY TO DECLARE
COSMETIC PRODUCTS TO THE PRODUCT REGISTERS
Data from the Nordic SPIN database illustrates an incomplete picture of the use of methyl- and
propylparaben in cosmetics in the Nordic countries. It is important to note that the duty to declare
products to the product registers does not apply to cosmetic products, and therefore these use
volumes do not cover the total use volume of parabens in cosmetics, but may give a rough estimate.
The use of the other 4 parabens are low compared to methyl- and propylparaben and therefore not
included in the figure. Figure 9 shows that the data in the Nordic SPIN database regarding the use
of parabens in cosmetic may not show the full picture. In 2010 only 12 products containing
propylparaben are registered in Denmark even though that consumer projects prepared by the
METHYLPARABEN PROPYLPARABEN
30 Survey of parabens
Danish EPA has shown that several products like sunscreen products and body lotions on the
Danish market contain parabens (etc. Tønnig et al, 2009; Andersen et al, 2012).
4.3.3 Use in food
Parabens have been added to food for more than 50 years and over the years, the use of parabens
has steadily increased to include many more food categories in USA (Soni et al, 2005), while in EU
the regulation regarding the use of parabens in food seems considerably stricter.
In USA parabens are employed in several foods including processed vegetables, baked goods, fats
and oils, seasonings, sugar substitutes, coffee extracts, fruit juices, pickles, sauces, soft drinks and
frozen dairy products at concentrations of between 450 and 2000 ppm (Soni et al, 2005), while in
Europe their use is restricted to confectionery (excluding chocolate) in amounts up to 300 mg
parabens/kg and as surface treatment of dry meat products, cereal- or potato-based snacks and
coated nuts (maximum 300 mg/kg) (Directive 2006/52/EC). In 2006 it was necessary to withdraw
the use of E216 propyl p-hydroxybenzoate and E217 sodium propyl p-hydroxybenzoate. (JECFA,
2006). Propylparaben could not be included in the group ADI because of effects on sex hormones
and the male reproductive organs in juvenile rats.
4.3.4 Use in pharmaceuticals
Parabens have a long history of use in drug products. They were first employed as preservatives in
pharmaceutical products in the mid-1920’s (Sabalitschka, 1930). Parabens have been incorporated
as preservatives in a variety of drug formulations. Combinations of parabens are more active than
individual parabens (Boehm and Maddox, 1972). Among the parabens, propyl paraben is one of the
most effective fungistats used in pharmaceutical products. A variety of drug formulations including
suppositories, anesthetics, pills, syrups, weight gaining solutions, injectable solutions and
contraceptives are known to contain parabens as preservatives (Soni et al, 2005).
In Denmark the main products preserved with parabens are oral mixtures/suspensions and
injection fluids and in minor product numbers creme formulations. It is primarily methyl- and
propylparaben that is used (personally contact to the Danish Health and Medicines Authority).
4.3.5 Use in other products
Parabens may be used as preservative in a broad range of products other than the three main uses
in cosmetics, food and pharmaceuticals.
According to information from the American homepage “household products database (U.S.
Department of Health & Human Services) parabens are also used in pet care products. The Nordic
SPIN database also shows small use in the category ‘paints, laquers, and varnishes’, ‘surface
treatments, and ‘anti-static agents’.
4.3.5.1 Cleaning/washing agents
Based on data from the SPIN database parabens (especially methyl- and propylparaben) are used as
preservative in cleaning products, washing products and dish washing products (machines). In
2010 around 1 tonnes of methylparaben was used in these kind of products in Sweden, while less
were used in the other Nordic countries, and it seems like the amount used in these products are
declining. The same trend is seen for propylparaben with a lower total amount (figure 10). However,
the number of products is not declining indicating the use of no or other substances as preservation
instead of paraben.
Survey of parabens 31
FIGURE 10 METHYLPARABEN AND PROPYLPARABEN USED IN CLEANING/WASHING AGENTS (NUMBER OF
PRODUCTS AND TOTAL AMOUNTS IN TONNES) ILLUSTRATED FOR SWEDEN, FINLAND, NORWAY AND DENMARK
4.3.5.2 Non-agricultural pesticides and preservatives (Biocides/in-can
preservatives)
According to data from the SPIN database (especially methyl- and propylparaben) used in non-
agricultural pesticides and preservatives. In 2010 around 27 tonnes of methylparaben was used in
these kinds of products in Sweden. Going into further details for this category the primary amount
is used as in-can preservatives. However, none of the 6 parabens are notified under the Biocides
Directive (98/8/EC), and therefore, they are not allowed to be used as in can preservatives. The
data from the SPIN database should therefore be investigated further to clarify, whether they may
be due to erroneous filing
FIGURE 11 METHYLPARABEN AND PROPYLPARABEN USED IN NON-AGRICULTURAL PESTICIDES AND
PRESERVATION (NUMBER OF PRODUCTS AND TOTAL AMOUNTS IN TONNES) ILLUSTRATED FOR SWEDEN,
FINLAND, NORWAY AND DENMARK
METHYLPARABEN PROPYLPARABEN
METHYLPARABEN PROPYLPARABEN
32 Survey of parabens
4.3.6 Estimated trends in use
The information found regarding the trend in production and/or use of parabens indicates that the
volume of use is decreasing. The data is mainly based on data from the Nordic SPIN database with
information from 1999 to 2010 (figure 1-8) and from the USA Non-confidential Inventory Update
Reporting production Volume information (table 10). However, the USA data is based on rather old
data from 1986 to 2002.
One could assume that the use would shift from use of longer chain parabens to short chain
parabens based on the massive press and discussions regarding especially propyl- and
butylparaben. However, the data identified shows, that there has been a decrease in use volumes for
both short- and long chain parabens. It has not been possible to identify 2011 and 2012 data, which
could confirm the decreasing trend seen from 2007 to 2010.
On the homepage of the Swedish Chemicals Agency (KemI) information on the trend in use was
retrieved (Figure 12). As cosmetic products and food are not included in KemI´s Product Register it
is not possible to find out whether use in cosmetics and food increases. On the other hand it is
possible to see that an increasing number of other chemical products, e.g. dish washing products,
are preserved with parabens. However, it seems that the volume (in tonnes) is increasing from the
beginning of the 90’s until the use volume is peaking in 2005-2006 and then declining from 2006
until 2010 for the products included in the products register. The level in 2010 is on the same level
as in 1999.
FIGURE 12 TURNOVER OF PARABENS IN CHEMICAL PRODUCTS EXCLUDING COSMETICS AND FOOD
(SOURCE: PRODUCTS REGISTER, SWEDISH CHEMICALS AGENCY, KEMI)
Survey of parabens 33
4.4 Conclusions Scarce information was received by the industry and authorities on total and application related use
volumes in and outside EU. Based on existing and available data retrieved from the internet, in view
of the general description of the substances, and especially in view of the numerous companies that
have pre-registrated the substances under REACH, the use in various products and the overall
amount of parabens appears to be substantial. World-wide the main use areas are cosmetic
products, pharmaceuticals and food. Based on the data found in this survey, methyl- and
propylparaben are the most widely used parabens with methylparaben showing the highest use
volume. Data on use from the Nordic countries product registers indicate that the use of parabens
has declined from 2006-2007, when the level peaked, until 2010. However, the use volume in 2010
was at the same level as in 1999.
34 Survey of parabens
5. Information on exposure
5.1 Occupational exposure Exposure may occur at manufacturing sites and production sites of cosmetics and other consumer
or chemical products containing parabens. Occupational exposure to parabens may occur through
inhalational exposure or through dermal contact, the latter generally being stated as the major
exposure route for the worker. Normally, oral exposure is not considered a significant route of
exposure in working situations.
5.2 Consumer exposure Exposure to parabens from consumer products can arise from the substances themselves, products
or articles containing the substance. As described in earlier chapters, parabens are widely used in
cosmetic products, pharmaceuticals and in food and thus human exposure to parabens is expected
to be widespread.
A literature search has been performed identifying papers on exposure to parabens. Several
biomonitoring studies describe that parabens are found in urine from pregnant Japanese women
and in Spanish and American women. Urinary excretion of free and total (free plus conjugated)
forms of methyl-, ethyl-, propyl- and butylparabens and their metabolite p-hydroxybenzoic acid
were measured for 111 pregnant Japanese women. Frequent detection of parabens and their
metabolite indicated that exposure takes place daily for pregnant Japanese women. The order of
total concentrations of the 4 parabens were methyl- > propyl- > ethyl- > butylparaben, which
concurs with the results of studies in the USA (Calafat et al, 2010) and Spain (Casas et al, 2011).
This indicates a similar usage in personal care products and/or foods in these countries and in
Japan (Sayaka et al, 2012), and confirms the pattern shown in chapter 4.2 that methyl- and
propylparaben are the mostly used parabens.
A study in Norway including 332 individuals found elevated levels of native paraben in plasma from
the general population. Methylparaben was the paraben found in highest amounts (median level of
9.4 ng/ml) and was detected in 63% of the samples. Propylparaben was detected in 29% of the
samples in a median concentration of less than 2 ng/ml. The authors found a strong and significant
association between the observed plasma levels of parabens with the use of skin care products
(Sandanger et al, 2011).
Depending of the nature of the products and its use different exposure routes may be relevant. The
different exposure routes are described for relevant product groups and exposure is estimated based
on literature information.
5.2.1 Cosmetics
The main exposure route from cosmetics is dermal. The USA Cosmetic Ingredient Expert Panel
estimated that skin metabolism of parabens is likely to result in as little as 1% of un-metabolized
parabens being available for absorption into the body (CIR, 2008), whereas the SCCS estimated
that 3.7% of intact propylparaben or butylparaben may be absorbed intact through the skin (SCCS,
2011). The issue regarding the amount of intact parabens absorbed though intact human skin is still
at discussion with new studies being performed (Frederiksen, 2011; Aubert et al, 2012). Aubert et
al, 2012) argue that dermal absorptions of 14.5% (for methylparaben) to 27.1% (for butylparaben)
measured in rat studies would project a human systemic exposure ranging from 0.5% to 9% taking
into account the high permeability of rat skin compared to human skin. Furthermore, they argue
Survey of parabens 35
that topical use of parabens does not produce a significant systemic exposure to the parent
compounds, but to a metabolite, i.e. para-hydroxybenzoic acid (PHBA).
Several approaches have been made to estimate the exposure for parabens from cosmetics:
• The SCCS has estimated an external aggregate exposure from cosmetic product of 69.6
mg/person/day, equal to 1.16 mg/kg bw/day (SCCS/1348/10). This is derived from an
estimated total use of cosmetic products of 17.4 g/person/day and a maximum concentration
of 0.4%. Using a dermal absorption of 3.7 % this leads to a systemic exposure of 0.043 mg/kg
bw/day.
• An adult human systemic dose of 1.18 mg/kg bw/day of multiple parabens (based on 50%
absorption through skin) and an infant systemic dose of 0.336 mg/kg bw/day (also based on
50% absorption through skin) was estimated by CIR from the use of average daily cosmetics of
17.76 gram of products per day for adults and 378 mg of products for infants (CIR, 2008).
• In a project funded by the Danish EPA “Exposure of pregnant consumers to suspected
endocrine disruptors“ an estimated systemic exposure of 0.089 mg/kg bw/day for each single
paraben as a worst-case exposure was found for propyl-, butyl- and isobutylparabens
(Andersen et al, 2012). This was estimated based on a scenario, where the cosmetic product
contained maximum 0.1% (as acid) propyl-, butyl- or isobutylparaben.
• Cumulative exposure was estimated to 1.3 mg/kg bw/day based on refined aggregate exposure
estimates in Cowan-Ellsberry and Robison, 2009. Of this, 0.79, 0.34, and 0.0016 mg/kg
bw/day was methyl-, propyl- and butylparaben, respectively.
5.2.2 Food
In the EU, the allowed content of methyl- and ethylparaben in food are maximum 300 mg
paraben/kg food (in total as methyl-or/and ethylparaben). EFSA has established a full-group ADI of
10 mg/kg bw for the sum of methyl and ethyl parabens and their sodium salts (Regulation (EU) No.
1129/2011).
In the US, some estimations of paraben exposure from food have been done. Two exposure
estimates for methyl- and propylparaben, the two parabens that are used most extensively in food
in the USA, have been done. The first approach was to use the disappearance data on the amount of
these parabens used each year. These data would estimate that an average person consumes as
much as 0.001 mg/kg/day of methylparaben in food and 0.013 mg/kg/day of propylparaben in food
assuming a body weight of 60 kg. The second approach uses Flavor Extract Manufacturer’s
Association (FEMA) estimates of Possible Average Daily Intake which employs the usual use levels
in products and mean consumption values for the various foods. The estimated exposure via food
using this approach is 0.004 mg/kg/day for both methyl- and propylparaben assuming a body
weight of 60 kg. It is important to note that these exposure estimates are based on USA data, were
the regulation of parabens in food are less strictly compared to the EU and that the estimations are
based on rather old use volume data from the 80’s. However, the estimation may give an impression
of the level of exposure.
The Danish Veterinary and Food Administration perform yearly control analyses of different kind of
foods for their content of parabens (See table 10).
36 Survey of parabens
TABLE 10 YEARLY CONTROL ANALYSES OF DIFFERENT KIND OF FOODS
Year Methyl- and Ethylparaben Propylparaben
2007 76 samples (fish pate, takeaway
dishes, spices, sauces)
75 samples (fish pate, takeaway
dishes, spices, sauces, pizza
filling, cakes, and marzipan)
2008 3 samples (fish pate, fish cake) 3 samples (fish pate, fish cake)
2009 2 samples (chocolate, potato
chips)
2 samples (chocolate, potato
chips)
2010 37 samples: (chocolate, potato
chips, cakes, marinades, sauce,
sausage, fish cakes, marzipan)
3 samples: (tomato sauce, pesto,
olive oil)
2011 4 samples: (olive oil, pesto,
tomato sauce)
4 samples: (olive oil, pesto,
tomato sauce)
2012 45 samples: (chocolate) 45 samples: (chocolate)
None of the analysed samples in table 10 contained methyl-, ethylparaben or propylparaben,
respectively.
In the project “Exposure of pregnant consumers to suspected endocrine disruptors “funded by the
Danish EPA the exposure to parabens from food were also included: However, the exposure to
parabens (propyl-, butyl- and isobutylparaben) from food was estimated to be negligible (Andersen
et al, 2012).
5.2.3 Pharmaceuticals
Exposure to parabens in pharmaceuticals may be via the oral, dermal, intravenously or inhalation
route depending on the pharmaceutical products intended use. Data to estimate the exposure is
available for Denmark (data received from the Danish Health and Medicines Authority). However,
it will be an extensive work to calculate the exposure, which is out of range of this project.
5.3 Human exposure via the environment Human exposure via the environment is considered as being minor. However, new studies indicate
that exposure may take place via indoor dust. In a study, 158 indoor dust samples from the US,
China, Korea, and Japan were collected and the concentrations of six parabens and their common
hydrolysis product, 4-hydroxybenzoic acid (4-HB) were determined. All of the target compounds
were found in dust samples from four countries. Concentrations of sum of six parabens in dust were
on the order of several hundred to several thousands of nanogram per gram. Methyl- and
propylparaben were the predominant compounds found in dust samples. Methylparaben accounted
for 42−73% of the total paraben concentrations, with mean concentrations ranging from 226 to
1670 ng/g. Propylparaben accounted for 12−46% of the total paraben concentrations, with mean
concentration range of 123−761 ng/g. On the basis of the measured concentrations of target
chemicals, an estimated daily intake (EDI) via dust ingestion was assessed. The EDIs of parabens
via dust ingestion were 5−10 times higher in children than in adults. Among the four countries
studied, the EDIs of parabens (5.4 ng/kg bw/day) through dust ingestion were the highest for
children in Korea and Japan. This is explained by the use of cosmetics in the four countries as the
consumption of cosmetics and skin care products by Korean and Japanese women was similar, which was five times higher than that reported for American women, and 50 times higher than that reported for Chinese women (Wang et al, 2012).
Survey of parabens 37
5.4 Conclusions Human exposure to parabens is mainly through cosmetic products. An older USA estimation of
exposure indicates that only 20% will be through food, making cosmetics the main exposure route
for humans. Of the exposure through cosmetics, almost 100% will be dermal. The health risk from
exposure to parabens in cosmetics has long been, and still is, the object of much discussion.
38 Survey of parabens
6. Environmental hazard and fate assessment
6.1 Monitoring The use of parabens as a preservative in food, cosmetics, pharmaceuticals and other chemical
products (cleaning agents e.g.) may result in its release to the environment through various waste
streams. Most ingredients in cosmetic products may eventually end up in the aquatic environment
through sewage treatment systems, either directly when they are used (e.g. soaps, toothpastes,
shampoos, hair dyes) or after use (wash-off during showering) (e.g. make-up, deodorants, hair-
styling products, perfumes). Some products/ingredients may also be released directly into the
environment (both the aquatic environment and air) upon use (e.g. sunscreen lotions, hair-styling
products, creams). In a study from Spain results showed the presence of methyl- and propylparaben
in sewage sludge at low ng/ g levels. The occurrence of parabens in sewage sludge was studied
analysing samples collected in three wastewater treatment plants during a period of four years.
Methylparaben and propylparaben were detected in three wastewater treatment plants throughout
the study and while methylparaben levels remained rather constant (5.1 to 26.2 ng/g dry weight) an
increase in the concentration of propylparaben was observed (levels up to 44.1 ng/g dry weight).
The study demonstrates that parabens can be found in sewage sludge from wastewater treatment
plants, although at low concentrations (ng/g levels) (Albero et al, 2012/in press). In Tokushima and
Osaka, in a Japanese study they found aquatic concentrations of seven parabens in urban streams
highly affected by treated or untreated domestic sewage. The detected highest concentrations were
670, 207, and 163 ng/l for methyl-, propyl- and butylparaben, respectively (Yamamoto et al, 2011).
6.2 Fate assessment 6.2.1 Air
If parabens are released to air, their estimated vapour pressure indicates that they will exist mainly
as a vapour in the atmosphere. They will be degraded in the atmosphere by reaction with
photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be
10 - 15 days (HSDB, 2007). However, no data on parabens measured in air were found.
6.2.2 Soil
If parabens are released to soil, they are expected to have from low to high mobility based upon
their estimated Koc ranging from 119 – 2100.
All parabens may readily biodegrade in the environment based on the biodegradation data of
methylparaben, which degraded 100% after 6 days using the Zahn-Wellens test which suggests that
biodegradation may be an important environmental fate process (HSDB, 2007).
6.2.3 Water
If released into water, methyl- and ethylparaben are not expected to adsorb to suspended solids and
sediment based upon the estimated log Koc (see Table 2). Propyl- and butylparaben, however, are
expected to adsorb to suspended solids and sediment based upon the estimated log Koc of 3.04 -
3.57 (see Table 3) (HSDB, 2007). No data is available for isopropyl- and isobutylparaben.
Based on the estimated Henry’s Law constant values for parabens (6.4 10-4 – 8.5 10-9 atm m3/mol)
volatilization from water surfaces is not expected to be an important fate process. An estimated
Survey of parabens 39
bioconcentration factor (BCF) of 6.4 and 16 for methyl- and ethylparaben respectively suggests that
the potential for bioconcentration in aquatic organisms is low for these two substances. An
estimated BCF of 44 for propylparaben suggests that the potential for bioconcentration in aquatic
organisms is moderate, while an estimated BCF of 110 for butylparaben suggests the potential for
bioconcentration in aquatic organisms is high. Hydrolysis is not expected to be an important
environmental fate process (HSDB, 2007).
6.3 Environmental hazard The Advisory list for self-classification (table 6) indicates a potential acute aquatic toxicity of
propyl- and butylparaben based on QSAR predictions. However, butylparaben was previously self-
classified as chronic aquatic toxic based on the QSAR calculations available at the time the LOUS
list was established. Results from acute and chronic toxicity studies in algae, daphnia and fish are
shown in figure 13.
FIGURE 13 RESULTS (µG/L) FROM ACUTE AND CHRONIC TOXICITY STUDIES IN ALGAE, DAPHNIA AND FISH
FOR 7 DIFFERENT PARABENS (TABLES COPIED FROM YAMAMOTO ET AL, 2011).
The data shows, that none of the tested parabens would be classified as acute or chronic toxic for
aquatic animals. The acute toxicity of methyl-, ethyl- and propylparaben in the study by Yamamoto
et al (2011) is comparable to previous studies by Madsen et al. (2001) and Dobbins et al. (2009).
Yamamoto et al (2011) measured environmental concentrations (MECs) of seven parabens in
40 Survey of parabens
Tokushima (maximum 676 ng/l) and Osaka (maximum 199 ng/l) and divided them by the predicted
no effect concentrations (PNECs). The risk ratio (MEC/PNEC) was determined for individual
parabens. The MEC/PNEC was highest for propylparaben (0.010) followed by butylparaben (max.
of 0.0086) and methylparaben (max. of 0.0042). The sum of the MEC/PNEC for seven parabens
was 0.0049 (Yamamoto et al, 2011).
It has been shown, that the longer chain parabens may have potential estrogenic effects on fish as
they induce the production of vitellogenin in rainbow trout after intraperitoneal injection at doses
of 100-300 mg/kg and/or after exposure in water containing propylparaben at a concentration of
225 µg/L (Petersen et al, 2000), (Bjerregaard et al, 2003).
6.4 Conclusion For the environment, the assessment of fate and hazard for parabens indicated a low toxicity. This
was despite the QSAR prediction on which the Advisory list for self-classification is based,
identifying propyl- and butylparaben as acute toxic to aquatic animals. Only few data regarding the
environmental toxicity of parabens were found. For the parabens, estimated risk ratios were
calculated as MEC/PNEC (measured environmental concentrations/predicted no effect
concentrations). The highest MEC/PNEC was (0.010) for propylparaben followed by butylparaben
(max. of 0.0086) and methylparaben (max. of 0.0042). These estimated low risk ratios (<<1) thus
indicate a low risk for environmental effects of parabens. Some studies have shown that parabens
may have estrogenic effects in fish. However, the effects are seen at concentrations much higher (µg
- mg) than actual environmental concentrations, as for instance in Spain and Japan (ng/L).
Survey of parabens 41
7. Human health hazard assessment
Acute, subchronic, and chronic studies in rodents generally indicate that parabens have a low
toxicological potential. In individuals with normal skin, parabens are for the most part non-
irritating and non-sensitizing. However, application of products containing parabens to damaged or
broken skin has resulted in sensitization. Genotoxicity testing of parabens in a variety of in vitro
and in vivo studies primarily gave negative results. The paraben structure is not indicative of
carcinogenic potential, and experimental studies support these observations (Elder, 1984; Soni et
al, 2005).
In 1984 the Cosmetic Ingredient Review (CIR) looked into the safety of methylparaben,
propylparaben, and butylparaben and concluded they were safe for use in cosmetic products at
levels up to 25%. Typically parabens are used at levels ranging from 0.01 to 0.3% (Elder, 1984). The
CIR is an industry-sponsored organization that reviews the safety of cosmetic ingredients and
publishes its results in open, peer-reviewed literature. In 2005, the CIR decided to re-open the
safety assessment for parabens and requested exposure estimates and a risk assessment for
cosmetic uses. In December 2005, the authors concluded that a high margin of safety exists for
human exposure to parabens despite reports of numerous endocrine-related effects of these
chemicals. This high safety margin was illustrated by an adult human dose of 1.2 mg/kg bw/day of
multiple parabens and an infant dose of 0.3 mg/kg bw/day when comparing with a no-observed
adverse effect level (NOAEL) of 1000 mg/kg bw/day for all parabens. The NOAEL was established
by CIR based on the most statistically, powerful and well-conducted study of the effects of
butylparaben on the male reproductive system, although adverse effects of butyl-, isobutyl-, propyl-,
ethyl-, and methylparaben at doses below 1000 mg/kg bw/day were reported by CIR.
Subsequently, the European Scientific Committee on Consumer Safety reviewed the parabens
(SCCS)1. The first SCCS Opinion (SCCP, 2005a) was performed in 2005 and addressed issues about
parabens and breast cancer from use of underarm cosmetics. The Opinion concluded that with the
current knowledge there is no evidence of a demonstrable risk for the development of breast cancer
caused by the use of underarm cosmetics.
Another Opinion (SCCP, 2005b) was published in 2005. This Opinion was an extensive evaluation
of the safety of parabens. This Opinion concluded that the maximum authorised concentration of
0.4% (as acid) for one ester and 0.8% (as acid) for a mixture of esters should be maintained for
methyl- and ethylparaben. SCCS also concluded that data for propyl-, isopropyl-, butyl- and
isobutylparaben were insufficient. An acceptable daily intake (ADI) of 10 mg/kg bw/day which was
determined for methyl- and ethylparaben by the European Food Safety Authority (EFSA) is
mentioned in the SCCS Opinion. The safety of those two parabens was considered well documented.
The SCCS did not find data sufficient for an assessment of the other parabens, and the EFSA was
also not able to determine an ADI for those parabens. The SCCS requested reproductive and
developmental toxicity studies and in vitro studies on percutaneous absorption on propyl-,
isopropyl-, butyl- and isobutylparaben.
1 Until February 2009 the Committee was called the European Scientific Committee on Consumer Products (SCCP)
42 Survey of parabens
Based on this request additional data was submitted to the SCCS, who made an evaluation of these
and published a new Opinion in 2006 (SCCP, 2006). SCCS concluded that there were still too many
shortcomings in data to change or modify the conclusions from the 2005 Opinion (SCCP, 2005b).
Based on this conclusion a hearing took place in which industry defended their submission. The
result of this hearing and a few new publications were discussed in a new Opinion from 2008
(SCCP, 2008). The conclusions remained the same; data were not sufficient to perform a safety
assessment of the long chained parabens, and industry was again encouraged to submit additional
data on reproductive toxicity and kinetics.
In 2010 the SCCS performed a safety assessment based on available data, even though it was stated
that those were not sufficient. A conservative NOEL of 2 mg/kg bw/day was chosen from a study
with butylparaben (Fisher, 1999) and the dermal absorption was set to 3.7%. The resulting margin
of safety pointed to unsafe use if the current concentration limits were used. Lowering the
maximum limit for propyl- and butylparaben to 0.14% (as acid) or 0.19% (as ester) would result in a
margin of safety of 100, which is considered to be adequate. The conclusion was therefore that
methyl- and ethylparaben are safe in the currently allowed concentrations whereas propyl- and
butylparaben are safe in a lower concentration. The isoforms of propyl- and butylparaben could not
be assessed based on existing data (SCCS, 2010).
In March 2011 Denmark issued a ban against propyl- and butylparaben in cosmetic products for
children under the age of 3 years. As a result of this, the SCCS made a clarification to its Opinion
from 2010 (SCCS, 2010) in October 2011 (SCCS, 2011). The conclusion in the 2011 Opinion was that
relevant human data on the metabolism of parabens are still lacking, and that these data are
required in order to reduce uncertainties in the assessment (SCCS, 2011). However, the SCCS also
concluded that for the time being there is no safety concern for children by using general cosmetics
that contain parabens, with the specific exception of products for the nappy area (SCCS, 2011).
In March 2012 a new study on the reproductive toxicity of propylparaben was presented to the
Working Group on Cosmetic Products (SCCS, 2012). The new study has a similar study design as
two former studies and does not demonstrate any reproductive effects on rats. The study has not
been published. Thus, this new study will result in an update of the 201o and 2011 Opinions on
propyl- and butylparaben. In addition, the new Opinion will take into account information on
exposure to sunscreens, especially for children below three years of age.
7.1 Absorption, metabolism, and excretion 7.1.1 Absorption
Overall, parabens are well absorbed after oral and subcutaneous administration (Aubert et al,
2012). It has also been argued that parabens are quickly and nearly completely hydrolysed into
para-hydroxybenzoic acid (PHBA) after dermal application to human skin, so the systemic
absorption of the parent compound is very low (Soni et al, 2005). However, other studies indicate
that the biotransformation of the different parabens into PHBA is not as efficient as claimed (Ye et
al, 2006; Janjua et al, 2007). The available in vitro dermal absorption studies are considered of
poor scientific quality by SCCS (2011), and the results of biomonitoring studies show the presence
of unmetabolised parabens in the plasma of human volunteers (Janjura et al, 2007; Sandanger et
al, 2011). According to SCCS (2010), data for the conversion from rat to human dermal absorption are still
lacking, especially for the absorption and metabolism of the parent compound in the skin.
As long as properly conducted dermal absorption and/or toxicokinetic studies in humans are not
available, the SCCS has established dermal absorption of parabens to be 3.7%. This value is derived
from the results of three in vitro dermal absorption studies (Fasano, 2004a, b; Fasano, 2005). The
value is based on a worst-case assumption for the dermal absorption of butylparaben, and it derives
from the mean dermal absorption of 37% measured in split-thickness skin (Fasano, 2004b), using a
Survey of parabens 43
correction factor of 10 to account for skin metabolism as seen in the full thickness skin experiments
(Fasano, 2004b, 2005).
7.1.2 Metabolism and Excretion
Parabens are excreted in urine as the metabolite PHBA or as conjugates of the parent compound
with either glycine, glucuronide or sulphate. Data indicates that parabens are not accumulated in
the body, and serum concentrations of parabens quickly decline and remain low (Boberg et al,
2010). Total levels of metabolites and parent compounds excreted in urine of orally and dermally
exposed rats and rabbits are high, indicating that parabens and/or their metabolites are taken up in
considerable amounts but rapidly metabolized and excreted (Boberg et al, 2010).
7.2 Estrogenic potential Concern has been raised about the endocrine disrupting potential of parabens at high exposure
levels. Studies in young male rats have shown adverse effects on sperm production and testosterone
levels following oral exposure to parabens with longer side chains, i.e. butyl- and propylparaben
(Oishi, 2001 and 2002). However studies with a similar design and of a more recent date do not
confirm these findings (Hoberman, 2008). Parabens are known to be estrogenic in vitro and in
uterotrophic assays in vivo, and estrogenicity appears to increase with side chain length (SCCS,
2011; Boberg et al, 2010).
However, there also seems to be a controversy about the endocrine disrupting potential of
parabens. The USA FDA finds that at the present time there is no reason for consumers to be
concerned about the use of cosmetics containing parabens. Although parabens can act similarly to
estrogen, they have been shown to have much less estrogenic activity than the body’s naturally
occurring estrogen. For example, a 1998 study (Routledge et al, 1998) found that the most potent
paraben tested butylparaben was 10,000- to 100,000-fold less active than naturally occurring
estradiol. Furthermore, the FDA states that parabens are used at very low levels in cosmetics. In a
review of the estrogenic activity of parabens, (Golden et al, 2005) the author concluded that based
on maximum daily exposure estimates, it was implausible that parabens could increase the risk
associated with exposure to estrogenic chemicals (FDA, 2007).
Methyl-, ethyl-, propyl- and butylparaben are on the EU list of potential endocrine disruptors which
are to be studied further for endocrine-disrupting properties (EU, 2012). They are entered as
category 1 substances, which are substances for which endocrine activity have been documented in
at least one study of a living organism. These substances are given the highest priority for further
studies. Furthermore, propyl- and butylparaben were both added to the SIN list (Substitute It Now)
at the latest update of that database (SIN list 2.0). The SIN project is an NGO-driven European
Union project to speed up the transition to a toxic-free world for the purpose of identifying
substances of very high concern, according to REACH criteria. Propyl- and butylparaben are
considered to belong to this category solely due to their potential endocrine disrupting properties.
7.2.1 Methyl- and ethylparaben
Methyl- and ethylparaben induced uterotrophic effects in immature rats and mice (Lemini et al,
2003). However, negative effects have also been seen for methyl- and ethylparaben (Hossaini et al,
2000). On the other hand, methyl- and ethylparaben were not shown to adversely affect the
secretion of sex hormones or male reproduction function up to about 1000 mg/kg bw/day (Oishi et
al, 2004). Generally, methyl- and ethylparaben are considered to have a much lower potential for
causing endocrine disrupting effects compared to propyl- and butylparaben (SCCS, 2005).
44 Survey of parabens
7.2.2 Propylparaben
Several studies have shown that propylparaben has estrogenic and/or antiandrogenic effects in vivo
and in vitro (described in SCCS’ Opinion 2010).Propylparaben is generally considered to be less
potent than butylparaben, both in vitro and in vivo (SCCS 2010). In screening studies for estrogenic
effects of propylparaben, 10-20 mg/kg bw/day (LOAEL) increased uterine weight (Lemini et al,
2003; Lemini et al,, 2004), and 10 mg/kg bw/day reduced epididymis weight and sperm production
in young rats (Oishi 2002). In a recent French study, juvenile rats were exposed by the oral route
(gavage) for 8 weeks post-weaning to propylparaben. These data are not published but are currently
being assessed by the SCCS. According to the SCCS mandate, the study does not confirm previous
conclusions about effects on reproduction (SCCS, 2012).
7.2.3 Butylparaben
The effects of butylparaben were investigated in a study by Fisher et al. (1999). Here, effects were
followed on the male reproductive system in young rats. A NOEL of 2 mg/kg bw/day was
determined in this study. Furthermore, reduced sperm count was observed in offspring of rats
exposed during pregnancy and lactation (Kang et al, 2002). No antiandrogenic effects, seen as
anogenital distance in males, were observed in studies with dosing during gestation (Kang et al,
2002, Boberg J, 2008; Taxvig C, 2008). In other studies, reduced sperm production has been
observed in young rats at 10-20 mg/kg bw/day (LOAEL) (Oishi, 2001), but subsequent studies with
the same study design have not shown the same type of effects (Hoberman AM, 2008). The
estrogenic effect is supported by findings of increased uterine weight in several screening studies for
estrogenic effect (Hossaini et al, 2000; Lemini et al, 2003; Lemini et al, 2004; Vo et al, 2009). A
few studies of estrogenic effects in immature animals show effects at the same low doses (Lemini et
al, 2003), while other studies only show effects at higher doses (Vo et al, 2009, Vo et al, 2010) or do
not examine the low doses (Hossaini et al, 2000).
7.2.4 Isopropyl- and isobutylparaben
Uterotrophic effects in immature rats have been observed for both isopropyl- and isobutylparaben
(Koda et al, 2005, Vo et al, 2009). A NOAEL of 62.5 mg isobutylparaben/kg bw/day was
determined for increased uterine weight in immature female mice and immature female rats,
respectively in screening studies for estrogenic effect (Darbre et al, 2002; Vo et al, 2009). Several
studies show estrogenic effect in corresponding in vivo studies and in cell-based studies, and
therefore it can be considered to be robust knowledge that isobutylparaben is an endocrine
disrupter (Koda et al, 2005). Fewer studies, compared to other parabens, have studied the
estrogenic potential of isopropylparaben. However, it is considered that isopropylparaben is an
endocrine disrupter (Vo et al, 2009).
7.2.5 Risk assessment considering the endocrine disrupting effects
The literature points out that the method for evaluating the endocrine disrupting potential of
parabens and the kinetics of the substances is still not agreed upon (e.g. CIR, 2008; Boberg et al,
2010; Witorsch and Thomas, 2010; SCCP, 2011; Scialli, 2011). Considering the endocrine disrupting
effects of parabens, a final risk assessment still awaits which NOEL/NOAEL to use and which
dermal absorption fraction to use.
7.2.6 Combination effects
The Danish EPA has lead two projects investigating the risks from combined exposure (exposure
from several sources) and risks from exposure to “cocktails” (exposures from several substances
with the same effect at the same time); one considering the exposure to infants, and one considering
the exposure to pregnant women (Tønning et al, 2009, Andersen et al, 2012). In these projects,
combined exposures to different parabens were investigated. However, the different assumptions
these projects were built upon are not the same, as one would assume if the projects were done
today. Thus, the results are not summarised in this report.
Survey of parabens 45
7.3 Conclusions Concerns have been raised about the endocrine disrupting potential of parabens at high exposure
levels. Some studies in young male rats have shown adverse effects on sperm production and
testosterone levels following oral exposure to parabens, i.e. propyl- and butylparaben. However
other studies with the same study design and of a more recent date did not confirm these finding
even at very high doses. Both the studies with positive and negative findings on reproductive
toxicity have shortcomings, which makes it difficult to assess and weigh the results. Parabens are
known to be estrogenic in vitro and in uterotrophic assays in vivo, and estrogenicity appears to
increase with side chain length. Therefore, methyl-, ethyl-, propyl- and butylparaben are on the EU
list of potential endocrine disruptors in category 1. Isopropyl- and isobutylparaben are not on this
EU list. Category 1 substances are substances for which endocrine disrupting activity has been
documented in at least one study of a living organism and are given the highest priority for further
studies.
This project reveals that the method for evaluating parabens for their endocrine disruption
potential and their kinetics are still not agreed upon. In addition, discussions on the most relevant
NOEL/NOAEL and the dermal absorption values have not yet come to a conclusion. Thus,
considering the endocrine disrupting effects, a final risk assessment still awaits which
NOEL/NOAEL to use and which dermal absorption fraction to use, and to further identify the
overall exposure for children. Currently a new study concerning reproductive toxicity is being
assessed by the SCCS. Only few studies are available on the combined exposure to several parabens
from several products.
46 Survey of parabens
8. Information on alternatives
From the industry no common alternatives are suggested. In cosmetic products other allowed
preservatives according to directive 76/768/EEC may be used. However, several of the alternative
preservatives are skin sensitizers.
Some vitamins and essential oils e.g. E-vitamin, tea tree oil and grape seed oil that may be used in
cosmetics have a preserving action without being added to the cosmetics with that purpose. In a
project regarding cosmetic products marketed as “non-preserved”, sponsored by the Danish EPA, it
was found that some non-preserved products contained fragrances in a concentration that has
antibacterial effect (Poulsen, 2011). The disadvantage in adding some natural substances with
preserving properties is, compared to parabens, that they may need to be added in high
concentration to give an effect as good as parabens, which again may result in more allergies.
The “paraben-history” has had a lot of focus in the press and in campaigns from e.g. the Danish EPA
which has led to a broad marketing of “paraben-free” cosmetics. The Danish EPA has through
several campaigns encouraged children below the age of three and pregnant women to use
“paraben-free” products (Danish EPA, 2010; 2012).
Initiatives have also been made toward changing the containers for cosmetics thereby to be able to
reduce/avoid the use of preservatives in cosmetics. Appropriate packaging like use of dispensing
mechanisms that make the entry of microorganisms into the product very difficult could be
successful. However, there were no applications to a recently launched funding programme from
the Danish EPA for technology development in this area (Danish EPA, 2012),
Some companies participating in this survey have indicated that alternatives are not possible at the
moment (in pharmaceuticals e.g.), but investigations in alternatives takes place in the companies.
The project group was not told what kind of alternatives the investigations include.
8.1 Conclusion Alternatives to the parabens could be preservatives that are approved for use in other areas.
However, before changing preservatives on a large scale, the sensitising potential of many other
preservatives must be borne in mind. Parabens themselves are rarely seen as sensitizers, although
some of the parabens have been self-classified as skin- or respiratory sensitizers. Technologies
totally reducing the need for preservation have not yet been marketed.
Survey of parabens 47
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• Regulation (EU) No 528/2012 of the European Parliament and of the Council of 22 May 2012
concerning the making available on the market and use of biocidal products
• Routledge EJ, Parker J, Odum J, Ashby J, Sumpter JP, (1998). Some alkyl hydroxyl benzoate
preservatives (parabens) are estrogenic. Toxicology and Applied Pharmacology, 153(1) pp 12-
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of parabens in postmenopausal women and self-reported use of personal care products: the
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• Savage, JH, Matsui, EC, Wood, RA, Keet, CA,; Urinary Levels of Triclosan and Parabens Are
Associated with Aeroallergen and Food Sensitization,", Journal of Allergy and Clinical
Immunology, Vol 130 ISs 2, pp 453-460, 2012
Available from: http://www.cosmeticsandtoiletries.com/research/biology/160819625.html.
• Sayaka Shirai, Yayoi Suzukia, Jun Yoshinagaa, Hiroaki Shiraishi, Yoshifumi Mizumotoc (2012)
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52 Survey of parabens
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54 Survey of parabens
Abbreviations
ADI Acceptable Daily Intake
AF Assessment Factor
B Bioaccumulation
BCF Bioconcentration Factor
BMC Benchmark Concentration
BMD Benchmark Dose
BMF Biomagnification Factor
bw body weight / Bw, bw
CA Chromosome Aberration
CA Competent Authority
CAS Chemical Abstract Services
CEN European Standards Organisation / European Committee for Normalisation
CEF Panel on food contact materials, enzymes, flavourings and processing aids
CMR Carcinogenic, Mutagenic and toxic to Reproduction
CNS Central Nervous System
CoRAP Community Rolling Action Plan
dw dry weight / dw
DG Directorate General
DNEL Derived No-Effect Level
EC European Communities
EC10 Effect Concentration measured as 10% effect
EC50 median Effect Concentration
ECB European Chemicals Bureau
ECETOC European Centre for Ecotoxicology and Toxicology of Chemicals
ECHA European Chemicals Agency
EDC Endocrine Disrupting Chemical
EEC European Economic Communities
EFSA European Food Safety Authority
EINECS European Inventory of Existing Commercial Chemical Substances
ELINCS European List of New Chemical Substances
EN European Norm
EPA Environmental Protection Agency (USA)
EU European Union
EUSES European Union System for the Evaluation of Substances [software tool in support of the
Technical Guidance Document on risk assessment]
FAO Food and Agriculture Organisation of the United Nations
FCM Food Contact Material
HPLC High Pressure Liquid Chromatography
IARC International Agency for Research on Cancer
IC Industrial Category
IC50 median Immobilisation Concentration or median Inhibitory Concentration
IUCLID International Uniform Chemical Information Database (existing substances)
IUPAC International Union for Pure and Applied Chemistry
Koc organic carbon normalised distribution coefficient
Kow octanol/water partition coefficient
Survey of parabens 55
Kp solids-water partition coefficient
L(E)C50 median Lethal (Effect) Concentration
LC50 median Lethal Concentration
LD50 median Lethal Dose
LEV Local Exhaust Ventilation
LOAEL Lowest Observed Adverse Effect Level
LOEC Lowest Observed Effect Concentration
LOEL Lowest Observed Effect Level
LOQ Limits Of Quantification
MOE Margin of Exposure
MOS Margin of Safety
MW Molecular Weight
N Dangerous for the environment (Symbols and indications of danger for dangerous
substances and preparations according to Annex II of Directive 67/548/EEC
n Number (and here the number of repeating units in the molecule)
NAEL No Adverse Effect Level
NAEOL No Adverse Effect Observed level
NOAEL No Observed Adverse Effect Level
NOEL No Observed Effect Level
NOEC No Observed Effect Concentration
NTP National Toxicology Program (USA)
O Oxidizing (Symbols and indications of danger for dangerous substances and preparations
according to Annex II of Directive 67/548/EEC)
OC Organic Carbon content
OECD Organisation for Economic Cooperation and Development
OEL Occupational Exposure Limit
P Persistent
PBT Persistent, Bioaccumulative and Toxic
PEC Predicted Environmental Concentration
pH Logarithm (to the base 10) (of the hydrogen ion concentration {H+}
PNEC Predicted No Effect Concentration
QSAR (Quantitative) Structure-Activity Relationship
R phrases Risk phrases according to Annex III of Directive 67/548/EEC
RC Risk Characterization
RCR Risk Characterization Ratio
RfD Reference Dose
S phrases Safety phrases according to Annex IV of Directive 67/548/EEC
SAR Structure-Activity Relationships
SETAC Society of Environmental Toxicology And Chemistry
SML Specific Migration Limit
SSD Species Sensitivity Distribution
STP Sewage Treatment Plant
T Toxic (Symbols and indications of danger for dangerous substances and preparations
according to Annex II of Directive 67/548/EEC)
TDI Tolerable Daily Intake
TG Test Guideline
TGD Technical Guidance Document
TNO The Netherlands Organisation for Applied Scientific Research
TRV Toxicity Reference Values
UC Use Category
UDS Unscheduled DNA Synthesis
UN United Nations
UNEP United Nations Environment Programme
56 Survey of parabens
US EPA Environmental Protection Agency, USA
UV Ultraviolet Region of Spectrum
vB very Bioaccumulative
VOC Volatile Organic Compound
vP very Persistent
vPvB very Persistent and very Bioaccumulative v/v volume per volume ratio
w/w weight per weight ratio
WHO World Health Organization
WWTP Waste Water Treatment Plant
Strandgade 29 1401 København K, Denmark Tlf.: (+45) 72 54 40 00
www. mst.dk
Survey of parabens
This survey is part of the Danish EPA’s review of the substances on the List of Undesirable
Substances (LOUS). The report defines the substances and present information on the use and
occurrence of parabens internationally and in Denmark, information on existing regulation, on
environmental and health effects, on monitoring and exposure, on waste management and on
alternatives to the substances.
Kortlægning af parabener
Denne kortlægning er et led i Miljøstyrelsens kortlægninger af stofferne på Listen Over Uønskede
Stoffer (LOUS). Rapporten definerer stofferne og indeholder blandt andet en beskrivelse af brugen
og forekomsten af parabener internationalt og i Danmark, om eksisterende regulering, en
beskrivelse af miljø- og sundhedseffekter af stofferne, af moniteringsdata, af affaldsbehandling samt
alternativer til stoffet.